Diaminopyrimidine derivatives and processes for the preparation thereof

ABSTRACT

The present invention provides a diaminopyrimidine derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof. The diaminopyrimidine derivative or its pharmaceutically acceptable salt functions as a 5-HT 4  receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility, one of the gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony.

This is a National Phase Application filed under 35 U.S.C. §371 as anational stage of PCT/KR2012/001423, filed on Feb. 24, 2012, anapplication claiming the benefit under 35 U.S.C. §119 of the KoreanApplication No. 10-2011-0016981, filed on Feb. 25, 2011 the content ofeach of which is hereby incorporated by reference in their entirety.

TECHNICAL FIELD

The present invention relates to a novel 5-HT₄ receptor agonist, morespecifically a novel diaminopyrimidine derivative or itspharmaceutically acceptable salt having an activity as a 5-HT₄ receptoragonist, a process for the preparation thereof, a pharmaceuticalcomposition comprising the same, and a use thereof.

BACKGROUND ART

Serotonin (5-hydroxytryptamine, 5-HT), one of the neurotransmitters, isbroadly distributed throughout human body including both the centralnervous system and the peripheral nervous system. Approximately 95% ofthe human body's total serotonin is found in the gastrointestinal tract,while about 5% thereof is found in the brain. Serotonin receptors arelocated in intestinal nerves, enterochromaffin cells, intestinal smoothmuscle, immune tissues, etc. Serotonin receptor subtypes include 5-HT₁,5-HT₂, 5-HT₃, 5-HT₄, 5-HT₅, 5-HT₆, and 5-HT₇. Interactions between thesevarious receptors and serotonin are linked to various physiologicalfunctions. Therefore, various researches have been performed fordeveloping therapeutic agents that are capable of interacting with aspecific serotonin subtype as a target. The researches includeidentification of 5-HT₄ receptors and active agents interactingtherewith (Langlois and Fischmeister, J. Med. Chem. 2003, 46, 319-344).

It has been found by the previous literatures that 5-HT₄ receptoragonists are useful for treating an abnormal gastrointestinal motility,i.e., dysfunction in gastrointestinal motility. The abnormalgastrointestinal motility may result in various disorders, for exampleirritable bowel syndrome (IBS), constipation, dyspepsia, delayed gastricemptying, gastroesophageal reflux disease (GERD), gastroparesis,post-operative ileus, intestinal pseudo-obstruction, drug-induceddelayed transit, etc.

Representative 5-HT₄ receptor agonists disclosed in prior arts includetegaserod (an aminoguanidine derivative, U.S. Pat. No. 5,510,353),prucalopride (a benzofuran carboxamide derivative, EP0445862), cisapride(a benzamide derivative, U.S. Pat. No. 4,962,115), mosapride(EP0243959), etc. These compounds are known as an agent stimulatinggastrointestinal motility.

DETAILED DESCRIPTION OF THE INVENTION Technical Problem

The present inventors found that a certain diaminopyrimidine derivativefunctions as a 5-HT₄ receptor agonist, and therefore can be usefullyapplied for preventing or treating dysfunction in gastrointestinalmotility.

Therefore, the present invention provides the above diaminopyrimidinederivative or its pharmaceutically acceptable salt, a process for thepreparation thereof, a pharmaceutical composition comprising the same,and a use thereof.

Technical Solution

According to an aspect of the present invention, there is provided a useof a diaminopyrimidine derivative or its pharmaceutically acceptablesalt for the manufacture of a medicament for preventing or treating adysfunction in gastrointestinal motility

According to another aspect of the present invention, there is provideda pharmaceutical composition for preventing or treating a dysfunction ingastrointestinal motility comprising a diaminopyrimidine derivative orits pharmaceutically acceptable salt as an active ingredient.

According to still another aspect of the present invention, there isprovided a diaminopyrimidine derivative or its pharmaceuticallyacceptable salt.

According to still another aspect of the present invention, there isprovided a process for preparing the diaminopyrimidine derivative or itspharmaceutically acceptable salt.

Advantageous Effects

The compound of the present invention, i.e., the diaminopyrimidinederivative or its pharmaceutically acceptable salt, functions as a 5-HT₄receptor agonist, and therefore can be usefully applied for preventingor treating dysfunction in gastrointestinal motility, one of thegastrointestinal diseases, such as gastroesophageal reflux disease(GERD), constipation, irritable bowel syndrome (IBS), dyspepsia,post-operative ileus, delayed gastric emptying, gastroparesis,intestinal pseudo-obstruction, drug-induced delayed transit, or diabeticgastric atony.

BEST MODE FOR CARRYING OUT THE INVENTION

As used herein, the term “alkyl” refers to a straight or branchedaliphatic hydrocarbon radical. For example, C₁-C₆ alkyl means a straightor branched aliphatic hydrocarbon having 1 to 6 carbon atoms, such asmethyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl,sec-butyl, tert-butyl, neopentyl, and isopentyl.

The term “alkoxy or alkyloxy” refers to a radical formed by substitutingthe hydrogen atom of a hydroxyl group with an alkyl. For example, C₁-C₆alkoxy includes methoxy, ethoxy, propoxy, n-butoxy, n-pentyloxy,isopropoxy, sec-butoxy, tert-butoxy, neopentyloxy, and isopentyloxy.

The term “alkenyl” refers to a straight or branched aliphatichydrocarbon radical having one or more double bond(s). For example,C₂-C₆ alkenyl includes ethenyl, propenyl, butenyl, pentenyl, andhexenyl.

The term “alkynyl” refers to a straight or branched aliphatichydrocarbon radical having one or more triple bond(s). For example,C₂-C₆ alkynyl includes ethynyl, propynyl, butynyl, pentynyl, andhexynyl.

The present invention provides a use of a compound of Formula 1 or itspharmaceutically acceptable salt for the manufacture of a medicament forpreventing or treating a dysfunction in gastrointestinal motility:

wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is a nitrogen-containing cyclic group selected from the groupconsisting of the following Formulas A to D (where * in Formulas A to Drepresents the position attached to the compound of Formula 1),

R₃ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₄ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or anoxo(═O) group,

R₅ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the following Formulas E to I(where * in Formulas E to I represents the position attached to one ofthe compounds of Formulas A to D),

R₆ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy,

X is —CH(R₇)—; —C(═O)—; —N(R₈)—; —O—; or —S—,

R₇ is hydrogen; a hydroxyl group; an aminocarbonyl group; a phenylgroup; or a C₁₋₅ alkyl group optionally substituted with piperidinyl orhydroxy,

R₄ and R₅, R₅ and R₆, R₄ and R₆, or R₅ and R₇ may be jointed each otherto form a pentagonal or hexagonal ring,

R₈ is hydrogen; a C₁₋₅ alkyl group; a C₁₋₅ alkoxycarbonyl group; aphenyl group optionally substituted with C₁₋₅ alkoxy or halogen,

R₉ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₁₀ is hydrgoen; or a C₁₋₅ alkyl group,

R₁₁ and R₁₂ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

In the use for the manufacture of a medicament for preventing ortreating a dysfunction in gastrointestinal motility according to thepresent invention, the dysfunction in gastrointestinal motility includesgastrointestinal diseases, such as gastroesophageal reflux disease(GERD), constipation, irritable bowel syndrome (IBS), dyspepsia,post-operative ileus, delayed gastric emptying, gastroparesis,intestinal pseudo-obstruction, drug-induced delayed transit, or diabeticgastric atony. The constipation includes chronic constipation, chronicidiopathic constipation (CIC), opioid-induced constipation (OIC), etc.And also, the dyspepsia includes functional dyspepsia.

In the use for the manufacture of a medicament for preventing ortreating a dysfunction in gastrointestinal motility according to thepresent invention, the compound or its salt may be the compound ofFormula 1 or its pharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is the nitrogen-containing cyclic group of Formula B,

R₃ is a C₁₋₅ alkyl group,

R₄ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;or an aminocarbonyl group,

R₅ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the Formulas E to I,

R₆, R₇, and R₁₀ are hydrogen,

X is —CH(R₇)—; —N(R₈)—; or —O—,

R₄ and R₅ may be jointed each other to form a pentagonal or hexagonalring,

R₈ is hydrogen; or a C₁₋₅ alkyl group,

R₉ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₁₁ and R₁₂ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

The present invention also provides a pharmaceutical composition forpreventing or treating a dysfunction in gastrointestinal motilitycomprising a therapeutically effective amount of a compound of Formula 1or its pharmaceutically acceptable salt; and a pharmaceuticallyacceptable carrier:

wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is a nitrogen-containing cyclic group selected from the groupconsisting of the following Formulas A to D (where * in Formulas A to Drepresents the position attached to the compound of Formula 1),

R₃ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₄ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or anoxo(═O) group,

R₅ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the following Formulas E to I(where * in Formulas E to I represents the position attached to one ofthe compounds of Formulas A to D),

R₆ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy,

X is —CH(R₇)—; —C(═O)—; —N(R₈)—; —O—; or —S—,

R₇ is hydrogen; a hydroxyl group; an aminocarbonyl group; a phenylgroup; or a C₁₋₅ alkyl group optionally substituted with piperidinyl orhydroxy,

R₄ and R₅, R₅ and R₆, R₄ and R₆, or R₅ and R₇ may be jointed each otherto form a pentagonal or hexagonal ring,

R₈ is hydrogen; a C₁₋₅ alkyl group; a C₁₋₅ alkoxycarbonyl group; aphenyl group optionally substituted with C₁₋₅ alkoxy or halogen,

R₉ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₁₀ is hydrgoen; or a C₁₋₅ alkyl group,

R₁₁ and R₁₂ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

In the pharmaceutical composition according to the present invention,the dysfunction in gastrointestinal motility includes gastrointestinaldiseases, such as gastroesophageal reflux disease (GERD), constipation,irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayedgastric emptying, gastroparesis, intestinal pseudo-obstruction,drug-induced delayed transit, or diabetic gastric atony. Theconstipation includes chronic constipation, chronic idiopathicconstipation (CIC), opioid-induced constipation (OIC), etc. And also,the dyspepsia includes functional dyspepsia.

In the pharmaceutical composition according to the present invention,the compound or its salt may be the compound of Formula 1 or itspharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is the nitrogen-containing cyclic group of Formula B,

R₃ is a C₁₋₅ alkyl group,

R₄ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;or an aminocarbonyl group,

R₅ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the Formulas E to I,

R₆, R₇, and R₁₀ are hydrogen,

X is —CH(R₇)—; —N(R₈)—; or —O—,

R₄ and R₅ may be jointed each other to form a pentagonal or hexagonalring,

R₈ is hydrogen; or a C₁₋₅ alkyl group,

R₉ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₁₁ and R₁₂ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

The pharmaceutical composition of the present invention may comprise apharmaceutically acceptable carrier, such as diluents, disintegrants,sweeteners, lubricants, or flavoring agents. The pharmaceuticalcomposition may be formulated to an oral dosage form such as tablets,capsules, powders, granules, suspensions, emulsions, or syrups; or aparenteral dosage form such as injection. The dosage form may be variousforms, e.g., dosage forms for single administration or for multipleadministrations.

The pharmaceutical composition of the present invention may comprise,for example, a diluent (e.g., lactose, corn starch, etc); a lubricant(e.g., magnesium stearate); an emulsifying agent; a suspending agent; astabilizer; and/or an isotonic agent. If necessary, the compositionfurther comprises sweeteners and/or flavoring agents.

The composition of the present invention may be administered orally orparenterally, including intravenous, intraperitoneal, subcutaneous,rectal and topical routes of administration. Therefore, the compositionof the present invention may be formulated into various forms such astablets, capsules, aqueous solutions or suspensions. In the case oftablets for oral administration, carriers such as lactose, corn starch,and lubricating agents, e.g. magnesium stearate, are conventionallyused. In the case of capsules for oral administration, lactose and/ordried corn starch can be used as a diluent. When an aqueous suspensionis required for oral administration, the active ingredient may becombined with emulsifying and/or suspending agents. If desired, certainsweetening and/or flavoring agents may be used. For intramuscular,intraperitoneal, subcutaneous and intravenous administration, sterilesolutions of the active ingredient are usually prepared, and the pH ofthe solutions should be suitably adjusted and buffered. For intravenousadministration, the total concentration of solutes should be controlledin order to render the preparation isotonic. The composition of thepresent invention may be in the form of an aqueous solution containingpharmaceutically acceptable carriers, e.g., saline having a pH level of7.4. The solutions may be introduced into a patient's intramuscularblood-stream by local bolus injection.

The compound of Formula 1 or its pharmaceutically acceptable salt may beadministered in a therapeutically effective amount ranging from about0.001 mg/kg to about 10 mg/kg per day to a subject patient. Of course,the dosage may be changed according to the patient's age, weight,susceptibility, symptom, or activity of the compound.

The present invention also provides a method for treating a dysfunctionin gastrointestinal motility, such as gastroesophageal reflux disease(GERD), constipation, irritable bowel syndrome (IBS), dyspepsia,post-operative ileus, delayed gastric emptying, gastroparesis,intestinal pseudo-obstruction, drug-induced delayed transit, or diabeticgastric atony, in a patient, which comprises administering atherapeutically effective amount of the compound of Formula 1 or itspharmaceutically acceptable salt to the patient in need thereof. Theconstipation includes chronic constipation, chronic idiopathicconstipation (CIC), opioid-induced constipation (OIC), etc. And also,the dyspepsia includes functional dyspepsia.

The present invention also provides a compound of Formula 1 or itspharmaceutically acceptable salt:

wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₃ alkyl (where the C₁₋₃ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl,benzimidazol-7-yl, benzoxazolyl, benzothiazolyl, and indazolyl, whereinthe heteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is a nitrogen-containing cyclic group selected from the groupconsisting of the following Formulas A to D (where * in Formulas A to Drepresents the position attached to the compound of Formula 1),

R₃ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₄ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group, an aminocarbonyl group; a formyl group; or anoxo(═O) group,

R₅ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the following Formulas E to I(where * in Formulas E to I represents the position attached to one ofthe compounds of Formulas A to D),

R₆ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy,

X is —CH(R₇)—; —C(═O)—; —N(R₈)—; —O—; or —S—,

R₇ is hydrogen; a hydroxyl group; an aminocarbonyl group; a phenylgroup; or a C₁₋₅ alkyl group optionally substituted with piperidinyl orhydroxy,

R₄ and R₅, R₅ and R₆, R₄ and R₆, or R₅ and R₇ may be jointed each otherto form a pentagonal or hexagonal ring,

R₈ is hydrogen; a C₁₋₅ alkyl group; a C₁₋₅ alkoxycarbonyl group; aphenyl group optionally substituted with C₁₋₅ alkoxy or halogen,

R₉ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₁₀ is hydrgoen; or a C₁₋₅ alkyl group,

R₁₁ and R₁₂ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

Preferably, the compound or its salt may be the compound of Formula 1 orits pharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₃ alkyl (where the C₁₋₃ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl,benzimidazol-7-yl, benzoxazolyl, benzothiazolyl, and indazolyl, whereinthe heteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is the nitrogen-containing cyclic group of Formula B,

R₃ is a C₂₋₅ alkyl group,

R₄ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;or an aminocarbonyl group,

R₅ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the Formulas E to I,

R₆, R₇, and R₁₀ are hydrogen,

X is —CH(R₇)—; —N(R₈)—; or —O—,

R₄ and R₅ may be jointed each other to form a pentagonal or hexagonalring,

R₈ is hydrogen; or a C₁₋₅ alkyl group,

R₉ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₁₁ and R₁₂ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

The compound of Formula 1 or its pharmaceutically acceptable salt mayhave substituents containing asymmetric carbon and therefore be in theform of racemic mixture (RS) or in forms of optical isomers, such as (R)or (S) isomer. The compound of Formula 1 or its pharmaceuticallyacceptable salt comprises both racemic mixture (RS) and optical isomerssuch as (R) or (S) isomer. And also, the compound of Formula 1 or itspharmaceutically acceptable salt may be in the form of cis- ortrans-geometrical isomer, according to substituents having e.g., thedouble bond therein. The compound of Formula 1 or its pharmaceuticallyacceptable salt comprises both cis- and trans-geometrical isomers. Andalso, the compound of Formula 1 or its pharmaceutically acceptable saltmay be in the form of one or more diastereomic isomer(s) or a mixturethereof. The compound of Formula 1 or its pharmaceutically acceptablesalt comprises both diastereomic isomer(s) and a mixture thereof.

The compound of Formula 1 of the present invention may be in apharmaceutically acceptable salt form. The salt may be an acid additionsalt form, which includes e.g., salts derived from an inorganic acidsuch as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfonicacid, sulfamic acid, phosphoric acid, or nitric acid; and salts derivedfrom an organic acid such as acetic acid, propionic acid, succinic acid,glycolic acid, stearic acid, citric acid, maleic acid, malonic acid,methanesulfonic acid, ethanesulfonic acid, tartaric acid, hydroxymaleicacid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid,2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid,benzenesulfonic acid, oxalic acid or trifluoroacetic acid. The salt maybe prepared by reacting a compound of Formula 1 in the form of free basewith a salt-forming inorganic or organic acid in stoichiometric amountor excessive amount, in a suitable solvent or a mixture of two or moresolvents.

In the use, the pharmaceutical composition, the treatment method, andthe compound according to the present invention, more preferablecompounds include a compound (or its pharmaceutically acceptable salt)selected from the group consisting of:

-   N-(4-fluorophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   4-(azepan-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-(2-methylpiperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-(3-methylpiperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-propyl-6-thiomorpholinopyrimidin-2-amine;-   4-(2,5-dimethylpiperazin-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   4-(5,6-dihydropyridin-1(2H)-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-(decahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-[decahydroisoquinolin-1(2H)-yl]-6-propylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-(piperazin-1-yl)-6-propylpyrimidin-2-amine;-   4-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   2-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   ethyl    1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-carboxylate;-   1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-4-carboxamide;-   {1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-4-yl}methanol;-   1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-4-one;-   4-butyl-N-(4-fluorophenyl)-6-(piperidin-1-yl)pyrimidin-2-amine;-   4-butyl-6-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)pyrimidin-2-amine;-   2-{1-[6-butyl-2-(4-fluorophenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;-   4-butyl-N-(4-fluorophenyl)-6-morpholinopyrimidin-2-amine;-   2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-(1-{2-[3-(methylthio)phenylamino]-6-propylpyrimidin-4-yl}piperidin-2-yl)ethanol;-   4-(2,6-dimethylmorpholino)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   8-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-8-azabicyclo[3.2.1]octan-3-ol;-   N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   N-(4-fluorophenyl)-4-{4-[3-(piperidin-4-yl)propyl]piperidin-1-yl}-6-propylpyrimidin-2-amine;-   4-[3-(benzyloxy)piperidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;-   N-(3-chloro-4-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;-   4-(piperidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-amine;-   N-[3-(methylthio)phenyl]-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(5-methoxy-2-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(5-chloro-2-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(4-fluoro-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(4-methoxyphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(3-methoxyphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(3-chlorophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(4-chloro-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   3-[4-(piperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   N-(4-methyl-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;-   4-(4-ethylpiperazin-1-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-[4-(4-methoxyphenyl)piperazin-1-yl]-6-methylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-[4-(4-fluorophenyl)piperazin-1-yl]-6-methylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-methyl-6-(morpholin-4-yl)pyrimidin-2-amine;-   1-[2-(4-fluorophenylamino)-6-methylpyrimidin-4-yl]piperidin-4-one;-   N-(4-fluorophenyl)-4-methyl-6-(piperidin-1-yl)pyrimidin-2-amine;-   4-(azetidin-1-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   1-[2-(4-fluorophenylamino)-6-methylpyrimidin-4-yl]piperidin-3-ol;-   1-[2-(4-fluorophenylamino)-6-methylpyrimidin-4-yl]piperidin-4-ol;-   N-(4-fluorophenyl)-4-methyl-6-(2-methylpiperidin-1-yl)pyrimidin-2-amine;-   N-(4-fluorophenyl)-4-methyl-6-(3-methylpiperidin-1-yl)pyrimidin-2-amine;-   4-(3,5-cis-dimethylpiperidin-1-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   4-(azepan-1-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   4-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   4-((2R,6S)-2,6-dimethylpiperidin-1-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-methyl-6-(4-phenylpiperidin-1-yl)pyrimidin-2-amine;-   N-(4-fluorophenyl)-4-methyl-6-(piperazin-1-yl)pyrimidin-2-amine;-   N-(4-fluorophenyl)-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine;-   4-(2,5-dimethylpiperazin-1-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   4-(3,5-dimethylpiperazin-1-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   N-(4-fluorophenyl)-4-methyl-6-(octahydroquinolin-1(2H)-yl)pyrimidin-2-amine;-   N-(4-fluorophenyl)-4-methyl-6-(octahydroisoquinolin-2(1H)-yl)pyrimidin-2-amine;-   4-(5,6-dihydropyridin-1(2H)-yl)-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine;-   2-{1-[2-(4-fluorophenylamino)-6-methylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(4-fluorophenylamino)-6-methylpyrimidin-4-yl]piperidin-2-yl}methanol;-   N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;-   2-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;-   N-(4-morpholino-6-propylpyrimidin-2-yl)-1H-indol-6-amine;-   N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;-   (R)-3-[4-(3-ethylmorpholino)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-tert-butyl    4-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]-3-methylpiperazin-1-carboxylate;-   (R)-3-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   4-morpholino-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;-   N-(4-fluoro-3-nitrophenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   N-(4-chloro-3-nitrophenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   N-(3-methoxyphenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   N-(4-methoxyphenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   N-[3-(methylthio)phenyl]-4-morpholino-6-propylpyrimidin-2-amine;-   N-(3-chlorophenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   N-(3-chloro-4-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   4-morpholino-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   N-(4-morpholino-6-propylpyrimidin-2-yl)-1H-indol-5-amine;-   N-(4-morpholino-6-propylpyrimidin-2-yl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine;-   N-(4-morpholino-6-propylpyrimidin-2-yl)quinolin-6-amine;-   3-(4-morpholino-6-propylpyrimidin-2-ylamino)benzonitrile;-   N-(5-methoxy-2-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   N-(5-chloro-2-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;-   N-(4-morpholino-6-propylpyrimidin-2-yl)quinolin-3-amine;-   4-(2-ethylpiperidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;-   4-(2-ethylpiperidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine;-   N-(4-chloro-3-nitrophenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;-   4-(2-ethylpiperidin-1-yl)-N-(3-methoxyphenyl)-6-propylpyrimidin-2-amine;-   4-(2-ethylpiperidin-1-yl)-N-(4-methoxyphenyl)-6-propylpyrimidin-2-amine;-   4-(2-ethylpiperidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine;-   N-(3-chlorophenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-(3-chloro-4-methylphenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;-   4-(2-ethylpiperidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;-   N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine;-   N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;-   3-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   4-(2-ethyl piperidin-1-yl)-N-(5-methoxy-2-methyl    phenyl)-6-propylpyrimidin-2-amine;-   N-(5-chloro-2-methyl phenyl)-4-(2-ethyl    piperidin-1-yl)-6-propylpyrimidin-2-amine;-   N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-3-amine;-   (R)—N-(4-chloro-3-nitrophenyl)-4-(2-methyl    piperazin-1-yl)-6-propylpyrimidin-2-amine;-   (R)—N-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;-   (R)—N-(2-methylpiperazin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   (R)—N-(2-methyl    piperazin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (R)—N-(4-fluoro-3-nitrophenyl)-4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-amine;-   (R)—N-(4-methyl-3-nitrophenyl)-4-(2-methyl    piperazin-1-yl)-6-propylpyrimidin-2-amine;-   (R)-4-fluoro-N¹-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine;-   (R)—N¹-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;-   (R)-2-fluoro-5-[4-(2-methyl    piperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-2-methyl-5-[4-(2-methyl    piperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-2-amino-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)—N¹-[4-(2-methyl    piperazin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;-   (R)-3-amino-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-3-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzamide;-   3-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   2-{1-[2-(1-ethyl-1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(1H-indol-5-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-(1-{6-propyl-2-[2-(trifluoromethyl)-1H-benzo[d]imidazol-6-ylamino]pyrimidin-4-yl}piperidin-2-yl)ethanol;-   2-{1-[2-(4-methoxyphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(3-methoxyphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(5-methoxy-2-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(2,3-dimethylbenzofuran-5-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[6-propyl-2-(quinolin-6-ylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(3-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   7-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-4-methyl-2H-chromen-2-one;-   2-{1-[6-propyl-2-(3-trifluoromethylphenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[6-propyl-2-(quinolin-3-ylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;-   (S)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   (S)-4-(3-aminopiperidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   (S)-5-{4-[3-(butylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-{4-[3-(pentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-{4-[3-(isobutylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-{4-[3-(isopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-2-methyl-5-{4-[3-(neopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-5-(4-{3-[(1H-pyrrol-2-yl)methylamino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;-   (S)-2-methyl-5-(4-propyl-6-{3-[(thiophen-2-ylmethyl)amino]piperidin-1-yl}pyrimidin-2-ylamino)benzonitrile;-   (S)-5-(4-{3[(4,5-dimethylfuran-2-ylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;-   (S)-2-methyl-5-{4-[3-(3-methylthiopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-{4-[3-(4-hydroxybenzylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   (S)-5-(4-{3-[bis(cyclopropylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;-   (R)-5-(4-{3-[bis(cyclopropylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;-   4-ethyl-N-(4-fluorophenyl)-6-(piperidin-1-yl)pyrimidin-2-amine;-   4-ethyl-N-(4-fluorophenyl)-6-(octahydroquinolin-1(2H)-yl)pyrimidin-2-amine;-   4-ethyl-6-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)pyrimidin-2-amine;-   2-{1-[6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;-   4-ethyl-N-(4-fluorophenyl)-6-morpholinopyrimidin-2-amine;-   2-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(4-amino-3-trifluoromethylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   2-fluoro-5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   2-amino-5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   2-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   2-{1-[2-(indolin-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   (S)-2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   (S)-2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   (R)-2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;-   3-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   N-(3-nitrophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(4-fluoro-3-nitrophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(4-chloro-3-nitrophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(3-methoxyphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(5-methoxy-2-methyl    phenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(4-methoxyphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   4-(octahydroquinolin-1(2H)-yl)-6-propyl-N-(3-trifluoromethyl    phenyl)pyrimidin-2-amine;-   N-(3-chlorophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(5-chloro-2-methylphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(3-chloro-4-methylphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-(3-methylthiophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;-   N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;-   N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-amine;-   N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;-   4-methyl-7-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amino]-2H-chromen-2-one;-   N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]quinolin-3-amine;-   (R)-5-{4-[3-(ethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-5-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-5-{4-[3-(butylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-2-methyl-5-{4-[3-(pentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (R)-5-{4-[3-(isobutylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-5-{4-[3-(isopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-2-methyl-5-{4-[3-(neopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (R)-5-{4-[3-(isopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-5-(4-{3-[(1H-pyrrol-2-yl)methylamino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;-   (R)-2-methyl-5-(4-propyl-6-{3-[(thiophen-2-ylmethyl)amino]piperidin-1-yl}pyrimidin-2-ylamino)benzonitrile;-   (R)-5-(4-{3-[(4,5-dimethylfuran-2-ylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;-   (R)-2-methyl-5-{4-[3-(3-methylthiopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (R)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-5-{4-[3-(cyclopentylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-5-{4-[3-(4-hydroxybenzylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;-   (R)-3-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (R)-3-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (R)-2-fluoro-5-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (R)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-fluorobenzonitrile;-   (R)—N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-4-fluorobenzene-1,3-diamine;-   (R)—N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;-   (R)-3-amino-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (R)—N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;-   (R)—N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine;-   (R)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[6-butyl-2-(4-methyl-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[6-butyl-2-(4-fluoro-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[6-butyl-2-(4-chloro-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(3-amino-5-trifluoromethylphenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(4-amino-3-trifluoromethylphenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[6-butyl-2-(4-fluoro-3-trifluoromethylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[6-butyl-2-(3-cyano-4-fluorophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(4-amino-3-cyanophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;-   (R)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;-   (R)—N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;-   (R)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;-   (R)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;-   (R)—N-(1-{2-[4-fluoro-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;-   (R)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;-   (R)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;-   (R)—N-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;-   (R)—N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;-   (R)-2-hydroxy-N-(1-{2-[4-methyl-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;-   (R)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;-   (R)-4-(3-aminopiperidin-1-yl)-N-(3-fluoro-4-methylphenyl)-6-propylpyrimidin-2-amine;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;-   (R)-3-amino-5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}benzonitrile;-   (R)-2-amino-5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}benzonitrile;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-chlorobenzene-1,3-diamine;-   (R)-4-(3-aminopiperidin-1-yl)-N-[4-methyl-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine;-   (R)—N-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;-   (R)-4-(3-aminopiperidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;-   (R)—N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   (R)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;-   (R)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;-   (R)—N-{1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-{1-[2-(4-fluoro-3-trifluoromethylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;-   (R)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;-   (R)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   (R)-2-fluoro-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-2-methyl-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)—N¹-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;-   (R)—N¹-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;-   (R)-3-amino-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-(4-fluoro-3-trifluoromethylphenyl)-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amine;-   (R)—N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;-   (R)—N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;-   (R)—N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;-   (R)—N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;-   (R)-3-amino-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   (R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-fluorobenzonitrile;-   (R)—N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;-   (S)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;-   (R)-5-({4-butyl-6-[3-(ethylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;-   (R)-5-({4-butyl-6-[3-(butylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;-   (R)-5-({4-butyl-6-[3-(pentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;-   (R)-5-({4-butyl-6-[3-(isobutylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;-   (R)-5-({4-butyl-6-[3-(isopentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;-   (R)-5-({4-butyl-6-[3-(neopentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;-   (R)-5-{[4-butyl-6-(3-{[3-(methylthio)propyl]amino}piperidin-1-yl)pyrimidin-2-yl]amino}-2-methylbenzonitrile;-   (R)-4-fluoro-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   (R)-4-chloro-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   (R)-2-amino-5-({4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}amino)benzonitrile;-   (R)—N-(3-methoxy-4-methylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;-   (R)-4-methyl-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   (R)-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;-   (R)-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-fluorobenzonitrile;-   (R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine;-   (R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;-   (R)-3-amino-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;-   (R)-2-amino-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;-   (R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-fluorobenzene-1,3-diamine;-   (R)-4-butyl-N-(3-methoxy-4-methylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;-   (R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-methylbenzene-1,3-diamine;-   (R)-4-butyl-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;-   (R)—N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;-   (R)—N-(3,4-dimethylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;-   (R)—N-(3-fluoro-4-methylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;-   (R)—N-[4-methyl-3-(trifluoromethyl)phenyl]-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;-   (R)-4-methoxy-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   (R)—N-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indazol-6-amine;-   (R)—N⁴-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,2,4-triamine;-   (R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;-   (R)-3-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;-   (R)-4-butyl-N-(3,4-dimethylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;-   (R)-4-butyl-N-(3-fluoro-4-methylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;-   (R)-4-butyl-N-[4-methyl-3-(trifluoromethyl)phenyl]-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;-   (R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-methoxybenzene-1,3-diamine;-   (R)—N-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-1H-indazol-6-amine;-   (R)—N⁴-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}benzene-1,2,4-triamine;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-nitrophenyl)pyrimidin-2-amine;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-fluoro-3-nitrophenyl)pyrimidin-2-amine;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;-   (R)-3-amino-5-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-[4-methyl-3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-fluoro-4-methylphenyl)pyrimidin-2-amine;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-methoxy-4-methylphenyl)pyrimidin-2-amine;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-4-methylbenzene-1,3-diamine;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3,4-dimethylphenyl)pyrimidin-2-amine;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-[4-fluoro-3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;-   (R)-2-amino-5-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;-   (R)-3-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;-   (R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]benzene-1,4-diamine;-   (R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-chloro-3-nitrophenyl)pyrimidin-2-amine;    and-   (R)—N⁴-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]benzene-1,2,4-triamine.

In the use, the pharmaceutical composition, the treatment method, andthe compound according to the present invention, still more preferablecompounds in terms of pharmacological activity include the compound (orits pharmaceutically acceptable salt) described in Table 2-1 and Table2-1.

The present invention includes, within its scope, a process forpreparing a compound of Formula 1 or its pharmaceutically acceptablesalt, which comprises reacting a compound of Formula 2 with a compoundof Formula 3 to obtain a compound of Formula 4; performing a methylationof the compound of Formula 4 to obtain a compound of Formula 5; reactingthe compound of Formula 5 with R₁—NH₂ to obtain a compound of Formula 6;performing a halogenation of the compound of Formula 6 to obtain acompound of Formula 7; and reacting the compound of Formula 7 with R₂—Hto obtain a compound of Formula 1:

wherein, R₁, R₂, and R₃ are the same as defined in the above; and Y ishalogen.

The compounds of Formula 2 and 3 are commercially available. Thereaction between the compound of Formula 2 and the compound of Formula 3may be performed in the presence of a base and a solvent. The base maybe potassium carbonate, sodium carbonate, etc and the solvent may be anaqueous solvent such as water. Typically, the reaction may be carriedout under heating.

The methylation of the compound of Formula 4 may be carried out using amethylating agent such as iodomethane. The methylation may be performedin the presence of a base and a solvent. The base may be sodiumhydroxide, potassium hydroxide, etc and the solvent may be an aqueoussolvent such as water. Typically, the methylation may be carried out atroom temperature or under heating.

The reaction between the compound of Formula 5 and R₁—NH₂ may beperformed in the absence of a solvent or in the presence of a solventsuch as diglyme. The reaction may be carried out at a temperatureranging from 140° C. to 180° C.

The halogenation of the compound of Formula 6 may be carried out using ahalogenating agent such as phosphorus oxychloride. The halogenation maybe performed preferably at a temperature of about 100° C. or higher. Andalso, for improving reaction rate and/or yield, the halogenation may beperformed in the presence of N,N-dimethylaniline orN,N-dimethylformamide in a catalytic amount.

The reaction between the compound of Formula 7 and R₂—H may be performedin the presence of an organic solvent, such as anhydroustetrahydrofuran, alcohol, and 1,4-dioxane. Typically, the reaction maybe carried out under heating. And also, for improving reaction rateand/or yield, the reaction may be performed in the presence of ametallic catalyst (e.g., palladium), a ligand, and a base such as cesiumcarbonate, isopropylethylamine; or performed under microwave rangingfrom 300 W to 600 W.

The compound of Formula 5 may be also prepared by reacting a compound ofFormula 2 with a compound of Formula 8:

wherein, R₃ is the same as defined in the above.

The compound of Formula 8 is commercially available. The reactionbetween the compound of Formula 2 and the compound of Formula 8 may beperformed in the presence of a base and a solvent. The base may bepotassium carbonate, sodium carbonate, etc and the solvent may be anaqueous solvent such as water. Typically, the reaction may be carriedout at room temperature or under heating.

The compound of Formula 6 may be also prepared by reacting a compound ofFormula 2 with a compound of Formula 9:

wherein, R₁ and R₃ are the same as defined in the above.

The compound of Formula 9 may be easily prepared by using known methods,e.g., EP0560726. The reaction between the compound of Formula 2 and thecompound of Formula 9 may be performed in the presence of a base and asolvent. The base may be sodium methoxide, sodium ethoxide, etc and thesolvent may be an alcohol. Typically, the reaction may be carried outunder heating.

The present invention also provides a process for preparing a compoundof Formula 1 or its pharmaceutically acceptable salt, which comprisesperforming a halogenation of a compound of Formula 4 to obtain acompound of Formula 10; reacting the compound of Formula 10 with R₂H toobtain a compound of Formula 11; and reacting the compound of Formula 11with R₁—NH₂ to obtain a compound of Formula 1:

wherein, R₁, R₂, and R₃ are the same as defined in the above; and Y ishalogen.

The halogenation of the compound of Formula 4 may be carried out using ahalogenating agent such as phosphorus oxychloride. The halogenation maybe performed preferably at a temperature of about 100° C. or higher. Andalso, for improving reaction rate and/or yield, the halogenation may beperformed in the presence of N,N-dimethylaniline orN,N-dimethylformamide in a catalytic amount.

The reaction between the compound of Formula 10 and R₂H may be performedin the presence of an organic solvent, such as anhydroustetrahydrofuran, alcohol, chloroform, or N,N-dimethylformamide.Typically, the reaction may be carried out at room temperature or underheating. And also, for improving reaction rate and/or yield, thereaction may be performed in the presence of a base such astriethylamine and diisopropylethylamine.

The reaction between the compound of Formula 11 and R₁—NH₂ may beperformed in the presence of an organic solvent such as alcohol,toluene, 1,4-dioxane, and N,N-dimethylformamide. The reaction may becarried out under heating. And also, for improving reaction rate and/oryield, the reaction may be performed in the presence of a metalliccatalyst (e.g., palladium), a ligand, and a base (e.g., cesiumcarbonate); or performed under microwave ranging from 300 W to 600 W.

The compound of Formula 10 may be also prepared by reacting a compoundof Formula 5 with an acid to obtain a compound of Formula 12; and thenperforming a halogenation of the compound of Formula 12:

wherein, R₃ and Y are the same as defined in the above.

The reaction between the compound of Formula 5 and the acid may beperformed using an organic acid (e.g., acetic acid, etc.) and aninorganic acid (e.g., hydrochloric acid, etc.). The reaction may beperformed in an aqueous solvent such as water. Typically, the reactionmay be carried out under heating.

The halogenation of the compound of Formula 12 may be carried out usinga halogenating agent such as phosphorus oxychloride. The halogenationmay be performed preferably at a temperature of about 100° C. or higher.And also, for improving reaction rate and/or yield, the halogenation maybe performed in the presence of N,N-dimethylaniline orN,N-dimethylformamide in a catalytic amount.

In accordance with an embodiment of the present invention, there isprovided a process for preparing a compound of Formula 1b or itspharmaceutically acceptable salt, which comprises reacting a compound ofFormula 1a with an organic acid or an acyl halide:

wherein, R₁, R₃, R₄, R₆, R₉, R₁₀, and X are the same as defined in theabove.

The reaction between the compound of Formula 1a and the organic acid maybe performed through amide coupling reaction, using a coupling agentsuch as (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphoniumhexafluorophosphate, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidehydrochloride, and 1-hydroxybenzotriazole hydrate; and a base such asdiisopropylethylamine or triethylamine. The coupling reaction may beperformed in an organic solvent such as dichloromethane, orN,N-dimethylformamide. Typically, the coupling reaction is performed atroom temperature.

And also, the reaction between the compound of Formula 1a and the acylhalide may be performed through amide coupling reaction, using anorganic base (e.g., diisopropylethylamine, triethylamine, etc) or aninorganic base (e.g., sodium hydroxide). The coupling reaction may beperformed in an organic solvent such as dichloromethane or a mixedsolvent of an organic solvent and water. Typically, the couplingreaction is performed at room temperature.

The compound of Formula 1b or its pharmaceutically acceptable salt maybe also prepared by reacting a compound of Formula 11a with an organicacid or an acyl halide to obtain a compound of Formula 11b; and thenreacting the compound of Formula 11b with R₁—NH₂ to obtain a compound ofFormula 1b:

wherein, R₁, R₃, R₄, R₆, R₉, R₁₀, and X are the same as defined in theabove; and Y is halogen.

The reaction between the compound of Formula 11a and the organic acidmay be performed through amide coupling reaction, using a coupling agentsuch as (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphoniumhexafluorophosphate, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidehydrochloride, and 1-hydroxybenzotriazole hydrate; and a base such asdiisopropylethylamine or triethylamine. The coupling reaction may beperformed in an organic solvent such as dichloromethane, orN,N-dimethylformamide. Typically, the coupling reaction is performed atroom temperature.

And also, the reaction between the compound of Formula 11a and the acylhalide may be performed through amide coupling reaction, using anorganic base (e.g., diisopropylethylamine, triethylamine, etc) or aninorganic base (e.g., sodium hydroxide, etc). The coupling reaction maybe performed in an organic solvent such as dichloromethane or a mixedsolvent of an organic solvent and water. Typically, the couplingreaction is performed at room temperature.

The reaction between the compound of Formula 11b and R₁—NH₂ may beperformed in an organic solvent such as alcohol, toluene, 1,4-dioxane,and N,N-dimethylformamide, etc. Typically, the reaction may be performedunder heating. And also, for improving reaction rate and/or yield, thereaction may be performed in the presence of a metallic catalyst (e.g.,palladium), a ligand, and a base (e.g., cesium carbonate); or performedunder microwave ranging from 300 W to 600 W.

In accordance with another embodiment of the present invention, there isprovided a process for preparing a compound of Formula 1c or itspharmaceutically acceptable salt, which comprises performing a reductiveamination using an aldehyde or a ketone with respect to a compound ofFormula 1a:

wherein, R₁, R₃, R₄, R₆, R₁₁, R₁₂, and X are the same as defined in theabove.

The reductive amination may be performed using a reducing agent such assodium borohydride, sodium triacetoxyborohydride, and sodiumcyanoborohydride. The reductive amination may be performed in an organicsolvent (e.g., alcohol) at room temperature or at low temperature (e.g.,at 0° C. or less). And also, for improving reaction rate and/or yield,the reaction may be performed in the presence of acetic acid, etc.

The compound of Formula 1c or its pharmaceutically acceptable salt maybe prepared by introducing an amine-protecting group to a compound ofFormula 11a to obtain a compound of Formula 11c; performing analkylation of the compound of Formula 11c to obtain a compound ofFormula 11d; and reacting a compound of Formula 11d with R₁—NH₂,followed by removing the amine-protecting group:

wherein, R₁, R₃, R₄, R₆, R₁₁, and X are the same as defined in theabove; Y is halogen; and R₁₂ is hydrogen. P is an amine-protecting groupsuch as tert-butoxycarbonyl.

The reaction for introducing an amine-protecting group to the compoundof Formula 11a may be performed in an organic solvent such asdichloromethane, chloroform, and 1,4-dioxane at room temperature or atlow temperature (e.g., at 0° C. or less). And also, the reaction may beperformed in the presence of a base such as triethylamine,diisopropylethylamine, and 4-dimethylaminopyridine.

The alkylation of the compound of Formula 11c may be performed using analkyl halide. The alkylation may be performed in the presence of a base(e.g., sodium hydride) in an organic solvent (e.g.,N,N-dimethylformamide). The alkylation may be performed at roomtemperature or under heating.

The reaction between the compound of Formula 11d with R₁—NH₂ may beperformed in an organic solvent such as alcohol, toluene, 1,4-dioxane,N,N-dimethylformamide. Typically, the reaction is performed underheating. And also, for improving reaction rate and/or yield, thereaction may be performed in the presence of a metallic catalyst (e.g.,palladium), a ligand, and a base (e.g., cesium carbonate); or performedunder microwave ranging from 300 W to 600 W. The reaction for removingthe amine-protecting group may be performed using an acid (e.g.,hydrochloric acid, trifluoroacetic acid, etc) in an organic solvent suchas ethyl acetate and methanol. Typically, the reaction may be performedat room temperature or at low temperature (e.g., at 0° C. or less).

The compound of Formula 11d may be also prepared by performing areductive amination with respect to a compound of Formula 11a to obtaina compound of Formula 11e; and then introducing an amine-protectinggroup to the compound of Formula 11e:

wherein, R₃, R₄, R₆, R₁₁, and X are the same as defined in the above; Yis halogen; and R₁₂ is hydrogen. P is an amine-protecting group such astert-butoxycarbonyl.

The reductive amination of the compound of Formula 11a may be performedusing a reducing agent such as sodium borohydride, sodiumtriacetoxyborohydride, and sodium cyanoborohydride. The reductiveamination may be in an organic solvent (e.g., alcohol) at roomtemperature or at low temperature (e.g., at 0° C. or less). And also,for improving reaction rate and/or yield, the reaction may be performedin the presence of acetic acid, etc.

The reaction for introducing an amine-protecting group to the compoundof Formula 11e may be performed in an organic solvent such asdichloromethane, chloroform, and 1,4-dioxane at room temperature or atlow temperature (e.g., at 0° C. or less). And also, the reaction may beperformed in the presence of a base such as triethylamine,diisopropylethylamine, and 4-dimethylaminopyridine.

The following examples and experimental examples are provided forillustration purposes only, and are not intended to limit the scope ofthe invention.

Preparation 1. 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine<Step 1> 2-(methylthio)-6-propylpyrimidin-4(3H)-one

A mixture of 6-n-propyl-2-thiouracil (25.0 g, 0.15 mol), sodiumhydroxide (5.9 g, 0.15 mol), iodomethane (10.2 ml, 0.17 mol), and water(300 ml) was stirred at room temperature overnight and then filtered.The resulting solid was dried in vacuo to give the titled compound (25.0g) as a white solid. The product was used in the subsequent reactionwithout further purification.

<Step 2> 2-(4-fluorophenylamino)-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (3.7 g, 0.02mol) prepared in Step 1 and 4-fluoroaniline (6.7 g, 0.06 mol) wasstirred at 160° C. overnight. The reaction mixture was cooled to roomtemperature, and then ethanol (50 ml) and charcoal (1 g) were addedthereto. The reaction mixture was stirred for 1 hour and then filtered.The filtrate was concentrated under reduced pressure. Ethanol (20 ml)was added to the resulting residue, which was then stirred for 1 hour.The reaction mixture was filtered to give the titled compound as a graysolid.

¹H-NMR (400 MHz, CD₃OD) δ 7.70-7.50 (m, 2H), 7.07 (t, 2H), 5.75 (s, 1H),2.43 (t, 2H), 1.70 (q, 2H), 0.98 (t, 3H)

<Step 3> 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine

2-(4-Fluorophenylamino)-6-propylpyrimidin-4(3H)-one (2.2 g, 8.9 mmol)prepared in Step 2 was added to phosphorus oxychloride (1.5 ml, 16.2mmol), which was then stirred at 110° C. for 5 hours. After cooling thereaction mixture to room temperature, an ice water was added to thereaction mixture, which was then basified to pH 9 with sodium hydroxide.The aqueous layer was extracted with ethyl acetate. The resultingorganic layer was dried on anhydrous sodium sulfate and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (ethyl acetate) to give 2.2 g ofthe titled compound as a yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 7.65-7.50 (m, 2H), 7.03 (t, 2H), 6.63 (s, 1H),2.60 (t, 2H), 1.75 (q, 2H), 0.99 (t, 3H)

Preparation 2. 4-butyl-6-chloro-N-(4-fluorophenyl)pyrimidin-2-amine<Step 1> 6-butyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one

A mixture of thiourea (2.4 g, 31.5 mmol), potassium carbonate (5.5 g,39.5 mmol), 3-oxoheptanoic acid ethyl ester (6.8 g, 39.5 mmol), andwater (40 ml) was stirred at 100° C. for 1 hour. After cooling thereaction mixture to room temperature, water (6 ml) and conc.hydrochloric acid (6 ml) were added to the reaction mixture, which wasthen extracted with ethyl acetate. The organic layer was concentratedunder reduced pressure. The resulting residue was washed with n-hexaneand then filtered. The resulting white solid was dried in vacuo to give1 g of the titled compound. The product was used in the subsequentreaction without further purification.

<Step 2> 6-butyl-2-(methylthio)pyrimidin-4(3H)-one

A mixture of 6-butyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (0.4 g, 2.2mmol) prepared in Step 1, sodium hydroxide (0.1 g, 2.2 mmol),iodomethane (0.15 ml, 2.4 mmol), and water (3 ml) was stirred at roomtemperature overnight and then filtered. The resulting white solid (0.2g) was dried in vacuo and then used in the subsequent reaction withoutfurther purification.

<Step 3> 6-butyl-2-(4-fluorophenylamino)pyrimidin-4(3H)-one

A mixture of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (0.16 g, 0.81mmol) in prepared in Step 2 and 4-fluoroaniline (0.28 g, 2.5 mmol) wasstirred at 160° C. overnight. After cooling the reaction mixture to roomtemperature, ethyl acetate (3 ml) was added thereto. The reactionmixture was stirred for 1 hour and then filtered to give 0.2 g of thetitled compound as a white solid.

¹H-NMR (400 MHz, CD₃OD) δ 7.70-7.50 (m, 2H), 7.07 (t, 2H), 5.75 (s, 1H),2.46 (t, 2H), 1.70-1.60 (m, 2H), 1.39 (q, 2H), 0.95 (t, 3H)

<Step 4> 4-butyl-6-chloro-N-(4-fluorophenyl)pyrimidin-2-amine

The titled compound (0.17 g) as a yellow oil was prepared in accordancewith the same procedures as in Step 3 of Preparation 1, using6-butyl-2-(4-fluorophenylamino)pyrimidin-4(3H)-one (0.2 g, 0.8 mmol)prepared in Step 3.

¹H-NMR (400 MHz, CDCl₃) δ 7.65-7.50 (m, 2H), 7.09 (brs, 1H), 7.03 (t,2H), 6.63 (s, 1H), 2.62 (t, 2H), 1.80-1.60 (m, 2H), 1.40 (q, 2H), 0.95(t, 3H)

Preparation 3.2-[1-(2-chloro-6-propylpyrimidin-4-yl)-piperidin-2-yl]ethanol <Step 1>2,4-dichloro-6-propylpyrimidine

Phosphorus oxychloride (100 ml) was slowly added to6-propyl-2-thiouracil (17.7 g, 0.1 mol) at room temperature, which wasthen stirred at 110° C. overnight. The reaction mixture was added to anice water and then neutralized with a saturated aqueous solution ofsodium bicarbonate. The reaction mixture was extracted withdichloromethane. The organic layer was dried on anhydrous magnesiumsulfate, filtered, and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=50/1) to give 10.3 g of the titled compound as apale yellow oil.

¹H-NMR (400 MHz, CDCl₃) δ 7.16 (s, 1H), 2.73 (t, 2H), 1.78 (m, 2H), 0.99(t, 3H)

<Step 2> 2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanol

2,4-Dichloro-6-propylpyrimidine (3 g, 15.7 mmol) prepared in Step 1 wasdissolved in chloroform (20 ml), and then 2-piperidineethanol (5.07 g,39.3 mmol) was added thereto at 0° C. The reaction mixture was stirredat 60° C. overnight and then cooled to room temperature. The reactionmixture was concentrated under reduced pressure. The resulting residuewas purified with silica gel column chromatography (n-hexane/ethylacetate=1/1) to give 2.3 g of the titled compound as a pale yellow oil.

¹H-NMR (400 MHz, CDCl₃) δ 6.27 (s, 1H), 4.92 (br, 1H), 3.83 (br, 1H),3.65 (m, 1H), 3.35 (m, 1H), 3.02 (m, 1H), 2.52 (m, 2H), 2.05 (m, 1H),1.79-1.62 (m, 6+2H), 1.53 (m, 1H), 0.96 (t, 3H)

Preparation 4. 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile<Step 1> 3-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (6.4 g, 34.7mmol) prepared in Step 1 of Preparation 1 and 3-aminobenzonitrile (12.3g, 104.1 mmol) was stirred at 160° C. overnight. The reaction mixturewas cooled to room temperature and then ethanol (50 ml) was addedthereto. The reaction mixture was stirred for 1 hour and then filteredto give 3.5 g of the titled compound as a pale brown solid.

¹H-NMR (400 MHz, CD₃OD) δ 8.22 (s, 1H), 7.90-7.80 (m, 1H), 7.55-7.45 (m,1H), 7.45-7.35 (m, 1H), 5.84 (s, 1H), 2.49 (t, 2H), 1.80-1.65 (m, 2H),1.00 (t, 3H)

<Step 2> 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile

3-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile (3.3 g,13.0 mmol) prepared in Step 1 was added to phosphorus oxychloride (10ml). The reaction mixture was stirred at 110° C. for 2 hours and thencooled to room temperature. The reaction mixture was added to an icewater and then basified to pH 9 with sodium hydroxide. The aqueous layerwas extracted with ethyl acetate. The resulting organic layer was driedon anhydrous sodium sulfate and then concentrated under reducedpressure. The resulting residue was purified with silica gel columnchromatography (n-hexane/ethyl acetate=10/1) to give 3.2 g of the titledcompound as a yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 8.18 (s, 1H), 7.75-7.65 (m, 1H), 7.50-7.20 (m,3H), 6.72 (s, 1H), 2.65 (t, 2H), 1.78 (q, 2H), 1.01 (t, 3H)

Preparation 5. 2-chloro-4-(piperidin-1-yl)-6-propylpyrimidine

2,4-dichloro-6-propylpyrimidine (2 g, 10.5 mmol) prepared in Step 1 ofPreparation 3 was dissolved in tetrahydrofuran (20 ml), and thenpiperidine (1 g, 11.7 mmol) was added thereto at room temperature. Thereaction mixture was stirred under heating at 60° C. overnight and thencooled to room temperature. The reaction mixture was concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (n-hexane/ethyl acetate=2/1) to give 2 g of thetitled compound as a pale yellow oil. The product was used in thesubsequent reaction without further purification.

Preparation 6. N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine<Step 1> 2-(1H-indol-6-ylamino)-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (1 g, 5.43 mmol)prepared in Step 1 of Preparation 1 and 6-aminoindole (789 mg, 5.97mmol) was stirred at 150° C. overnight and then cooled to roomtemperature. The resulting residue was purified with silica gel columnchromatography (dichloromethane/methanol=40/1) to give 1.4 g of thetitled compound as a pale brown solid.

¹H-NMR (400 MHz, CD₃OD) δ 7.81 (s, 1H), 7.51 (d, 1H), 7.21 (d, 1H), 6.95(dd, 1H), 6.42 (d, 1H), 5.70 (s, 1H), 2.44 (dd, 1H), 1.75-1.70 (m, 2H),0.99 (t, 3H).

<Step 2> N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine

A solution of 2-(1H-indol-6-ylamino)-6-propylpyrimidin-4(3H)-one (1.2 g,4.47 mmol) prepared in Step 1, phosphorus oxychloride (822 mg, 5.37mmol), and diisopropylethylamine (1.9 ml, 10.7 mmol) in 1,4-dioxane (45ml) was refluxed under stirring for 30 minutes. The reaction mixture wascooled to room temperature and then concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=4/1) to give 1.1 g of the titled compound as awhite solid.

¹H-NMR (400 MHz, CDCl₃) δ 8.17 (brs, 1H), 8.05 (s, 1H), 7.53 (d, 1H),7.25 (d, 1H), 7.11 (dd, 1H), 6.98 (dd, 1H), 6.58 (s, 1H), 6.48 (s, 1H),2.59 (dd, 2H), 1.81-1.71 (m, 2H), 0.99 (t, 3H).

Preparation 7.5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile <Step 1>2-methyl-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (5 g, 27.1 mmol)prepared in Step 1 of Preparation 1 and 5-amino-2-methylbenzonitrile (7g, 53 mmol) was stirred at 160° C. overnight. The reaction mixture wascooled to room temperature and then ethanol (30 ml) was added thereto.The reaction mixture was stirred for 1 hour and then filtered to give6.3 g of the titled compound as a pale yellow solid.

¹H-NMR (400 MHz, CD₃OD) δ 8.12 (d, 1H), 7.70-7.60 (m, 1H), 7.35 (d, 1H),5.80 (s, 1H), 2.50-2.40 (m, 5H), 1.73 (q, 2H), 0.99 (t, 3H)

<Step 2> 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile

2-Methyl-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile(6.3 g, 23.5 mmol) prepared in Step 1 was added to phosphorusoxychloride (10 ml). The reaction mixture was stirred at 110° C. for 2hours and then cooled to room temperature. The reaction mixture wasadded to an ice water and then basified to pH 9 with sodium hydroxide.The aqueous layer was extracted with ethyl acetate. The resultingorganic layer was dried on anhydrous sodium sulfate and thenconcentrated under reduced pressure to give 6 g of the titled compoundas a yellow solid. The product was used in the subsequent reactionwithout further purification.

Preparation 8.5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile <Step 1>2-fluoro-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (8.8 g, 47.8mmol) prepared in Step 1 of Preparation 1 and5-amino-2-fluorobenzonitrile (7.9 g, 57.2 mmol) was stirred at 160° C.overnight. The reaction mixture was cooled to 70° C. and then ethanol(50 ml) was added thereto. The reaction mixture was stirred for 1 hourand then filtered to give 10 g of the titled compound as a pale brownsolid. The product was used in the subsequent reaction without furtherpurification

<Step 2> 5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile

The titled compound (10.8 g) as a pale brown solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 4, using2-fluoro-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile(10 g, 36.7 mmol) prepared in Step 1.

¹H-NMR (400 MHz, CDCl₃) δ 8.20-8.10 (m, 1H), 7.75-7.65 (m, 1H),7.30-7.10 (m, 2H), 6.72 (s, 1H), 2.64 (t, 2H), 1.77 (q, 2H), 1.00 (t,3H)

Preparation 9. 4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine<Step 1> 6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-ol

A mixture of ethylpropionyl acetate (1.03 ml, 7.18 mmol),N-(4-fluorophenyl)guanidine (1 g, 6.53 mmol), sodium methoxide (0.39 g,7.18 mmol), and ethanol (30 ml) was refluxed under stirring overnight.The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was dissolvedin water, acidified to pH 4 with a 1N hydrochloric acid solution, andthen filtered. The resulting white solid (0.82 g) was dried in vacuo andthen used in the subsequent reaction without further purification.

<Step 2> 4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine

6-Ethyl-2-(4-fluorophenylamino)-pyrimidin-4-ol (0.82 g, 3.52 mmol)prepared in Step 1 was added to phosphorus oxychloride (1.5 ml, 16.2mmol), which was then stirred at 110° C. for 1 hour. After cooling thereaction mixture to room temperature, the reaction mixture was added toan ice water and then basified to pH 9 with potassium hydroxide. Theaqueous layer was extracted with dichloromethane. The resulting organiclayer was dried on anhydrous sodium sulfate and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (ethyl acetate/n-hexane=2/1) to give 432.2 mg ofthe titled compound as a white solid.

¹H-NMR (400 MHz, CDCl₃) δ 7.18 (m, 2H), 7.08 (m, 2H), 6.63 (s, 1H), 2.61(m, 2H), 1.23 (t, 3H)

Preparation 10. 4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine<Step 1> 2-(4-fluorophenylamino)-6-methylpyrimidin-4-ol

The titled compound (8.2 g) was prepared in accordance with the sameprocedures as in Step 1 of Preparation 9, using ethyl acetoacetate (10g, 76.8 mmol), N-(4-fluorophenyl)guanidine (10.7 g, 69.8 mmol) andsodium methoxide (4.2 g, 7.18 mmol). The product was used in thesubsequent step without further purification.

<Step 2> 4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine

The titled compound (4.5 g) in the form of white solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 9, using2-(4-fluorophenylamino)-6-methylpyrimidin-4-ol (8.2 g, 37.4 mmol)prepared in Step 1 and phosphorus oxychloride (15.9 ml, 172.0 mmol).

¹H-NMR (400 MHz, CDCl₃) δ 7.57-7.54 (m, 2H), 7.21 (brs, 1H), 7.05-7.01(m, 2H), 6.64 (s, 1H), 2.39 (s, 3H)

Preparation 11. 4-(2-chloro-6-propylpyrimidin-4-yl)morpholine

2,4-dichloro-6-propylpyrimidine (1 g, 5.23 mmol) prepared in Step 1 ofPreparation 3 and morpholine (683 mg, 7.85 mmol) were dissolved inethanol (30 ml). The reaction mixture was stirred at room temperaturefor 4 hours and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(n-hexane/ethyl acetate=2/1) to give 550 mg of the titled compound.

¹H-NMR (400 MHz, CD₃OD) δ 6.22 (s, 1H), 3.75 (d, 4H), 3.55 (d, 4H), 2.54(dd, 1H), 1.76-1.66 (m, 2H), 0.99 (t, 3H)

Preparation 12. 3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile<Step 1> 6-butyl-2-(methylthio)pyrimidin-4(3H)-one

A solution of ethyl 3-oxoheptanoate (10 g, 58.1 mmol),2-methyl-2-thiopseudourea sulfate (11.7 g, 63.9 mmol), and sodiumcarbonate (9.8 g, 92.9 mmol) in water (116 ml) was stirred at roomtemperature for 2 days and then filtered. The resulting white solid waswashed with water, and then dried in vacuo to give the titled compound(11 g). The product was used in the subsequent step without furtherpurification.

<Step 2> 3-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A solution of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (500 mg, 2.52mmol) prepared in Step 1 and 3-aminobenzonitrile (298 mg, 2.52 mmol) inn-butanol (3 ml) was stirred at 170° C. overnight. The reaction mixturewas cooled to room temperature and then purified with silica gel columnchromatography (dichloromethane/methanol=50/1) to give 310 mg of thetitled compound as a brown solid.

¹H-NMR (400 MHz, CDCl₃) δ 9.47 (brs 1H), 8.27 (s, 1H), 7.80 (d, 1H),7.37 (d, 1H), 5.88 (s, 1H), 2.58 (dd, 2H), 1.74-1.70 (m, 2H), 1.46-1.40(m, 2H), 0.98 (t, 3H)

<Step 3> 3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 9, using3-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)benzonitrile prepared inStep 2 and phosphorus oxychloride.

¹H-NMR (400 MHz, CDCl₃) δ 8.19 (s, 1H), 7.69 (d, 1H), 7.42 (t, 1H), 7.33(d, 1H), 7.26 (brs, 1H), 6.72 (s, 1H), 2.67 (t, 2H), 1.80-1.65 (m, 2H),1.50-1.30 (m, 2H), 0.97 (t, 3H); (Yield: 80%)

Preparation 13.5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile <Step 1>5-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)-2-methylbenzonitrile

A mixture of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (800 mg, 4.03mmol) prepared in Step 1 of Preparation 12 and5-amino-2-methylbenzonitrile (586 mg, 4.44 mmol) was stirred at 170° C.for 6 hours. The reaction mixture was cooled to room temperature andthen purified with silica gel column chromatography(dichloromethane/methanol=100/1) to give 650 mg of the titled compoundas a brown solid.

¹H-NMR (400 MHz, CDCl₃) δ 9.45 (brs 1H), 8.10 (s, 1H), 7.63 (d, 1H),7.25 (d, 1H), 5.78 (s, 1H), 2.55-2.48 (m, 5H), 1.70-1.65 (m, 2H),1.44-1.37 (m, 2H), 0.98 (t, 3H)

<Step 2> 5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 9, using5-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)-2-methylbenzonitrileprepared in Step 1 and phosphorus oxychloride.

¹H-NMR (400 MHz, CDCl₃) δ 8.08 (d, 1H), 7.57 (dd, 1H), 7.25 (m, 2H),6.69 (s, 1H), 2.65 (dd, 2H), 2.51 (s, 3H), 1.75-1.68 (m, 2H), 1.45-1.36(m, 2H), 0.96 (t, 3H); (Yield: 85%)

Preparation 14. 2-chloro-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidine

A solution of 2,4-dichloro-6-propylpyrimidine (1 g, 5.23 mmol) preparedin Step 1 of Preparation 3,2-ethylpiperidine (888 mg, 7.85 mmol),diisopropylethylamine (1.8 ml, 10.46 mmol) in chloroform (52 ml) wasstirred at 60° C. overnight. The reaction mixture was cooled to roomtemperature and then extracted with dichloromethane. The organic layerwas dried on anhydrous sodium sulfate and then filtered. The filtratewas concentrated under reduced pressure. The resulting residue waspurified with silica gel column chromatography (n-hexane/ethylacetate=10/1) to give 700 mg of the titled compound as a white solid.

Preparation 15. (R)-tert-butyl4-(2-chloro-6-propylpyrimidin-4-yl)-3-methylpiperazin-1-carboxylate

A solution of 2,4-dichloro-6-propylpyrimidine (0.8 g, 4.19 mmol)prepared in Step 1 of Preparation 3, (R)-tert-butyl3-methylpiperazine-1-carboxylate (0.92 g, 4.61 mmol), anddiisopropylethylamine (1.5 ml, 8.38 mmol) in chloroform (52 ml) wasstirred at 60° C. overnight. The reaction mixture was concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (n-hexane/ethyl acetate=4/1) to give 1.3 g of thetitled compound as a colorless liquid.

¹H-NMR (400 MHz, CD₃OD) δ 6.21 (s, 1H), 4.47-3.90 (m, 4H), 3.25-2.96 (m,3H), 2.54 (dd, 1H), 1.75-1.66 (m, 2H), 1.49 (s, 9H), 1.21 (d, 3H), 0.96(t, 3H)

Preparation 16. 2,5-diaminobenzonitrile

A mixture of 5-nitroanthranilonitrile (200 mg, 1.23 mmol) andpalladium/charcoal (10 mg, 10 wt %) in methanol (3 ml) was stirred atroom temperature under hydrogen atmosphere overnight and then filteredthrough a celite pad. The resulting filtrate was concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (n-hexane/ethyl acetate=1/2) to give 160.3 mg ofthe titled compound as a pale yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.79 (d, 1H), 6.72 (s, 1H), 6.61 (d, 1H), 4.01(brs, NH), 3.45 (brs, NH)

Preparation 17.(S)-2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanol

A solution of 2,4-dichloro-6-propylpyrimidine (300 mg, 1.57 mmol)prepared in Step 1 of Preparation 3, (S)-2-piperidineethanolhydrochloride (286 mg, 1.73 mmol) and triethylamine (460 μl, 3.30 mmol)in N,N-dimethylformamide (7 ml) was stirred at 80° C. overnight. Thereaction mixture was cooled to room temperature and then concentratedunder reduced pressure. The resulting residue was dissolved in ethylacetate. The solution was washed with water, dried on anhydrous sodiumsulfate, and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(n-hexane/ethyl acetate=2/5) to give 251.7 mg of the titled compound asa colorless oil.

¹H-NMR (400 MHz, CDCl₃) δ 6.29 (s, 1H), 4.91 (brs, 1H), 3.87 (brs, 1H),3.62 (m, 1H), 3.36 (m, 1H), 3.01 (m, 1H), 2.52 (t, 2H), 2.07 (m, 1H),1.69 (m, 6H), 1.51 (m, 1H), 0.96 (t, 3H)

Preparation 18.(R)-2-[1-(2-chloro-6-propylpyrimidin-4-yl)-piperidin-2-yl]ethanol

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as Preparation 17, using2,4-dichloro-6-propylpyrimidine prepared in Step 1 of Preparation 3 and(R)-2-piperidineethanol hydrochloride.

¹H-NMR (400 MHz, CDCl₃) δ 6.28 (s, 1H), 4.92 (brs, 1H), 3.86 (brs, 1H),3.62 (m, 1H), 3.35 (m, 1H), 3.01 (m, 1H), 2.52 (t, 2H), 2.07 (m, 1H),1.69 (m, 6H), 1.51 (m, 1H), 0.96 (t, 3H); (Yield: 32%)

Preparation 19. 1-(2-chloro-6-propylpyrimidin-4-yl)decahydroquinoline

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as Preparation 17, using2,4-dichloro-6-propylpyrimidine prepared in Step 1 of Preparation 3 anddecahydroquinoline.

¹H-NMR (400 MHz, CDCl₃) δ 6.03 (s, 1H), 4.46 (m, 1H), 3.09 (m, 2H), 2.53(t, 2H), 2.07 (d, 1H), 1.86-1.65 (m, 9H), 1.45-1.13 (m, 5H), 0.97 (t,3H); (Yield: 34%)

Preparation 20. (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-ylcarbamate

2,4-Dichloro-6-propylpyrimidine (1.5 g, 7.85 mmol) prepared in Step 1 ofPreparation 3 was dissolved in ethanol (10 ml) and then(3S)-(−)-3-(tert-butoxycarbonylamino)piperidine (3 g, 15.7 mmol) wasadded thereto at 0° C. The reaction mixture was stirred at roomtemperature overnight and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1) to give 1.1 g of the titled compound as awhite solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.29 (s, 1H), 4.58 (br, 1H), 3.78-3.41 (m,6H), 2.52 (t, 2H), 1.98 (m, 1H), 1.75 (br, 1H), 1.71 (m, 2H), 1.60 (s,9H), 0.95 (t, 3H); (Yield: 75%)

Preparation 21. 1-ethyl-1H-indol-6-amine <Step 1>1-ethyl-6-nitro-1H-indole

6-Nitroindole (200 mg, 1.23 mmol) was dissolved in anhydrousN,N-dimethylformamide (2 ml) and then 60 wt % sodium hydride (71 mg,1.85 mmol) and iodoethane (120 μl, 1.48 mmol) was added thereto at 0° C.The reaction mixture was stirred at room temperature overnight. Waterwas added to the reaction mixture, which was then extracted with ethylacetate. The organic layer was washed with brine, dried on anhydrousmagnesium sulfate, filtered, and then concentrated under reducedpressure to give 210 mg of the titled compound as a pale yellow solid.The product was used in the subsequent reaction without furtherpurification.

<Step 2> 1-ethyl-1H-indol-6-amine

To 1-ethyl-6-nitro-1H-indole (210 mg, 1.1 mmol) prepared in Step 1, wasadded a methanol/water solution (1:1; 5 ml). Iron (25 mg) and ammoniumchloride (127 mg, 2.38 mmol) were added to the resulting suspension,which was then refluxed under stirring for 4 hours. After cooling thereaction mixture to room temperature, an aqueous solution of sodiumcarbonate was added to the reaction mixture, which was then stirred for30 minutes. The reaction mixture was filtered through a celite pad. Theresulting filtrate was concentrated under reduced pressure to give 100mg of the titled compound as a pale yellow oil. The product was used inthe subsequent reaction without further purification.

Preparation 22. 2,3-dimethylbenzofuran-5-amine <Step 1>3-(4-nitrophenoxy)-butan-2-one

Acetone (16 ml) and 3-chloro-2-butanone (1.75 ml, 17.3 mmol) were addedto a mixture of 4-nitrophenol (2 g, 14.4 mmol), potassium carbonate (6g, 43.2 mmol), and potassium iodide (40 mg), which was then refluxedunder stirring for 10 hours. The reaction mixture was cooled to roomtemperature and then filtered through a celite pad. The resultingfiltrate was concentrated under reduced pressure. The resulting residuewas purified with silica gel column chromatography (n-hexane/ethylacetate=10/1) to give 2.1 g of the titled compound as a pale yellow oil.

<Step 2> 2,3-dimethyl-5-nitrobenzofuran

3-(4-Nitrophenoxy)-butan-2-one (2.1 g, 0.01 mol) prepared in Step 1 wasdissolved in toluene (20 ml) and then polyphosphoric acid (50 g) wasadded thereto. The reaction mixture was stirred at 100° C. for 5 hoursand then cooled to room temperature. Water was added to the reactionmixture, which was then extracted with diethyl ether. The organic layerwas dried on anhydrous sodium sulfate, filtered, and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (n-hexane/ethyl acetate=5/1) to give 1.8 g ofthe titled compound as a pale yellow oil.

<Step 3> 2,3-dimethyl benzofuran-5-amine

2,3-Dimethyl-5-nitrobenzofuran (1.8 g, 9.3 mmol) prepared in Step 2 wasdissolved in a mixed solvent of methanol and tetrahydrofuran (1:1, 50ml) and then palladium/charcoal (1.5 g) was added thereto. The reactionmixture was stirred at room temperature under hydrogen atmosphere (30bar) for 3 hours and then filtered through a celite pad. The resultingfiltrate was concentrated under reduced pressure to give 1.5 g of thetitled compound as a pale yellow solid. The product was used in thesubsequent reaction without further purification.

Preparation 23. (R)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl(cyclopropylmethyl)carbamate<Step 1> (R)-1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-amine

Diisopropylethylamine (9.1 ml, 52.2 mmol) was added to a solution of2,4-dichloro-6-propylpyrimidine (3.31 g, 17.3 mmol) prepared in Step 1of Preparation 3 and (R)-(−)-3-aminopiperidine dihydrochloride (3 g,17.3 mmol) in ethanol (90 ml), which was then stirred at 50° C.overnight. The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The product was used in thesubsequent reaction without further purification.

<Step 2>(R)-1-(2-chloro-6-propylpyrimidin-4-yl)-N-(cyclopropylmethyl)piperidin-3-amine

A solution of (R)-1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-amine(510 mg, 2.01 mmol) prepared in Step 1 and cyclopropane carboxaldehyde(0.15 ml, 2.01 mmol) in methanol (10 ml) was stirred at room temperaturefor 1 hour and then sodium triacetoxyborohydride (850 mg, 4.02 mmol) wasadded thereto. The reaction mixture was stirred at room temperatureovernight and then an aqueous saturated solution of sodium bicarbonatewas added thereto so as to terminate the reaction. The reaction mixturewas extracted with dichloromethane. The organic layer was washed with anaqueous saturated solution of sodium bicarbonate, dried on anhydroussodium sulfate, filtered, and then concentrated. The resulting residuewas purified with silica gel column chromatography (ethylacetate/methanol=50/1) to give 360 mg of the titled compound as a yellowoil.

¹H-NMR (400 MHz, CDCl₃) δ 6.10 (s, 1H), 4.24-3.92 (m, 2H), 2.97 (t, 1H),2.79 (t, 1H), 2.53 (m, 1H), 2.41 (m, 4H), 1.91 (m, 1H), 1.65 (m, 1H),1.57 (m, 2H), 1.41-1.21 (m, 3H), 0.83 (m, 4H), 0.37 (d, 2H), 0.00 (d,2H)

<Step 3> (R)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl(cyclopropylmethyl)carbamate

Di-tert-butyldicarbonate (307 mg, 1.41 mmol) was added at 0° C. to asolution of(R)-1-(2-chloro-6-propylpyrimidin-4-yl)-N-(cyclopropylmethyl)piperidin-3-amine(360 mg, 1.17 mmol) prepared in Step 2 and 4-dimethylaminopyridine (29mg, 0.24 mmol) in dichloromethane (6 ml). The reaction mixture wasstirred at room temperature overnight and then dichloromethane was addedthereto. The reaction mixture was washed with a 1N hydrochloric acidsolution, dried on anhydrous magnesium sulfate, and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (ethyl acetate/n-hexane=1/3) to give 218 mg ofthe titled compound as a yellow oil.

¹H-NMR (400 MHz, CD₃OD) δ 6.27 (s, 1H), 4.45-4.32 (brs, 2H), 3.42 (m,2H), 3.24-3.04 (m, 2H), 2.81 (m, 1H), 2.53 (m, 2H), 2.26 (m, 1H), 2.01(m, 1H), 1.69 (m, 2H), 1.55 (s, 9H), 1.26 (m, 2H), 1.07 (m, 1H), 0.96(t, 3H), 0.61 (m, 2H), 0.29 (m, 2H)

Preparation 24.(R)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]acetamide <Step1> 6-butylpyrimidin-2,4-diol

A mixture of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (2.1 g, 10.6mmol) prepared in Step 1 of Preparation 12, acetic acid (15 ml) andwater (7 ml) was refluxed under stirring for 2 days. The reactionmixture was cooled to room temperature and then concentrated underreduced pressure. The resulting residue was dried in vacuo to give 1.7 gof the titled compound as a pale yellow solid.

¹H-NMR (400 MHz, DMSO-d₆) δ 10.87 (brs, OH), 10.78 (brs, OH), 5.31 (s,1H), 2.27 (m, 2H), 1.50 (m, 2H), 1.27 (m, 2H), 0.88 (t, 3H)

<Step 2> 4-butyl-2,6-dichloropyrimidine

A mixture of 6-butylpyrimidin-2,4-diol (1.7 g, 10.2 mmol) prepared inStep 1 and phosphorus oxychloride (5 ml) was refluxed under stirring for1 hour. The reaction mixture was cooled to room temperature, added to anice water, and then basified to pH 8 with sodium bicarbonate. Theaqueous layer was extracted with ethyl acetate. The resulting organiclayer was dried on anhydrous magnesium sulfate and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (ethyl acetate/n-hexane=1/50) to give 1.4 g ofthe titled compound as a brown oil.

¹H-NMR (400 MHz, CDCl₃) δ 7.16 (s, 1H), 2.75 (t, 2H), 1.71 (m, 2H), 1.40(m, 2H), 0.95 (t, 3H)

<Step 3> (R)-1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-amine

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as in Step 1 of Preparation 23,using 4-butyl-2,6-dichloropyrimidine prepared in Step 2 and(R)-(−)-3-aminopiperidine dihydrochloride. The product was used in thesubsequent reaction without further purification.

<Step 4>(R)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]acetamide

Acetyl chloride (0.36 ml, 5.1 mmol) was added at 0° C. to a solution of(R)-1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-amine (1.2 g, 4.6mmol) prepared in Step 3 and triethylamine (0.96 ml, 6.9 mmol) indichloromethane (30 ml). The reaction mixture was stirred at roomtemperature for 3 hours and then dichloromethane was added thereto. Thereaction mixture was washed with water, dried on anhydrous magnesiumsulfate, and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography (ethylacetate/n-hexane=5/1) to give 0.8 g of the titled compound as a whitesolid.

¹H-NMR (400 MHz, CDCl₃) δ 6.31 (s, 1H), 5.60 (brs, NH), 3.98 (m, 1H),3.85-3.82 (m, 2H), 3.54-3.42 (m, 2H), 2.55 (t, 2H), 1.98 (s, 3H+1H),1.66-1.57 (m, 3H+2H), 1.36 (m, 2H), 0.93 (t, 3H)

Preparation 25.(R)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]-2-hydroxyacetamide

A mixture of (R)-1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-amine(1.33 g, 5.23 mmol) prepared in Step 1 of Preparation 23, glycolic acid(0.44 g, 5.79 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidehydrochloride (1.1 g, 5.79 mmol), 1-hydroxybenzotriazole hydrate (0.78g, 5.79 mmol), diisopropylethylamine (1.8 ml, 10.3 mmol), anddichloromethane (30 ml) was stirred at room temperature for 3 days. Thereaction mixture was diluted with dichloromethane, washed with water andan aqueous saturated solution of sodium bicarbonate, dried on anhydroussodium sulfate, and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(dichloromethane/methanol=20/1) to give 0.6 g of the titled compound asa white solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.57 (s, NH), 6.31 (s, 1H), 4.11 (s, 2H), 4.04(m, 1H), 3.90 (m, 2H), 3.49 (m, 3H), 2.53 (m, 2H), 2.40 (m, 1H), 2.00(m, 1H), 1.70-1.69 (m, 4H), 0.95 (m, 3H)

Preparation 26. (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]carbamate

Di-tert-butyldicarbonate (410 mg, 1.88 mmol) was added at 0° C. to asolution of (R)-1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-amine(400 mg, 1.57 mmol) prepared in Step 1 of Preparation 23 andtriethylamine (2.63 ml, 1.88 mmol) in 1,4-dioxane (10 ml). The reactionmixture was stirred at room temperature overnight and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (ethyl acetate/n-hexane=1/3) to give 440 mg ofthe titled compound as a pale yellow solid.

¹H-NMR (400 MHz, CD₃OD) δ′ 6.29 (s, 1H), 4.60 (brs, 1H), 3.90-3.30 (m,4H), 2.52 (t, 2H), 2.00-1.90 (m, 1H), 1.85-1.50 (m, 5H), 1.45 (s, 9H),0.95 (t, 3H)

Preparation 27. (R)-tert-butyl[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]carbamate

Di-tert-butyl dicarbonate (6.4 g, 29.3 mmol) was added at roomtemperature to a solution of(R)-1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-amine (6.6 g, 24.4mmol) prepared in Step 3 of Preparation 24, triethylamine (4.1 ml, 29.3mmol) in 1,4-dioxane (100 ml). The reaction mixture was stirredovernight and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/6) to give 7 g of the titled compound as apale yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.29 (s, 1H), 6.59 (m, 1H), 4.12 (m, 2H), 3.79(m, 1H), 3.68 (m, 1H), 3.56 (m, 1H), 3.40 (m, 1H), 2.54 (m, 2H), 1.98(m, 1H), 1.74 (m, 1H), 1.63 (m, 4H), 1.45 (s, 9H), 1.32 (m, 2H), 0.93(t, 3H)

Preparation 28. (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](methyl)carbamate

Sodium hydride (114 mg, 2.96 mmol, 60 wt %) was added at 0° C. to asolution of (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl)]carbamate (700 mg,1.97 mmol) prepared in Preparation 26 in N,N-dimethylformamide (2 ml).The reaction mixture was stirred for 30 minutes and iodomethane (184 μl,2.28 mmol) was added thereto. The reaction mixture was stirred at roomtemperature overnight and then water was added thereto. The reactionmixture was concentrated under reduced pressure. The resulting residuewas dissolved in ethyl acetate. The solution was washed with water,dried on anhydrous sodium sulfate, and then concentrated under reducedpressure. The resulting residue was purified with silica gel columnchromatography (n-hexane/ethyl acetate=5/1) to give 550 mg of the titledcompound as a white solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.25 (s, 1H), 4.31 (m, 2H), 4.11 (m, 1H), 2.90(m, 1H), 2.83 (s, 3H), 2.74 (m, 1H), 2.53 (m, 2H), 1.94-1.89 (m, 2H),1.76 (m, 3H), 1.48 (s, 9H), 0.96 (t, 3H)

Preparation 29. (R)-tert-butyl[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl](methyl)carbamate

Sodium hydride (344 mg, 8.95 mmol, 60 wt %) was added at 0° C. to asolution of (R)-tert-butyl[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl](methyl)carbamate (2.2g, 5.96 mmol) prepared in Preparation 27 in N,N-dimethylformamide (40ml). The reaction mixture was stirred for 30 minutes and iodomethane(558 μl, 8.95 mmol) was added thereto. The reaction mixture was stirredat room temperature overnight and then water was added thereto. Thereaction mixture was concentrated under reduced pressure. The resultingresidue was dissolved in ethyl acetate. The solution was washed withwater, dried on anhydrous sodium sulfate, and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (n-hexane/ethyl acetate=5/1) to give 2.1 g of thetitled compound as a white solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.25 (s, 1H), 4.40-4.26 (m, 2H), 3.84 (br,1H), 2.93 (m, 1H), 2.83 (s, 3H), 2.71 (m, 1H), 2.55 (m, 2H), 1.91 (m,2H), 1.77 (m, 1H), 1.66 (m, 2H), 1.49 (s, 9H), 1.41 (m, 2H), 0.95 (t,3H)

Preparation 30. (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](ethyl)carbamate

Sodium hydride (114 mg, 2.96 mmol, 60 wt %) was added at 0° C. to asolution of (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl)]carbamate (700 mg,1.97 mmol) prepared in Preparation 26 in N,N-dimethylformamide (2 ml).The reaction mixture was stirred for 30 minutes and iodoethane (237 μl,2.28 mmol) was added thereto. The reaction mixture was stirred at roomtemperature overnight and then water was added thereto. The reactionmixture was concentrated under reduced pressure. The resulting residuewas dissolved in ethyl acetate. The solution was washed with water,dried on anhydrous sodium sulfate, and then concentrated under reducedpressure. The resulting residue was purified with silica gel columnchromatography (n-hexane/ethyl acetate=5/1) to give 510 mg of the titledcompound as a white solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.26 (s, 1H), 4.32 (m, 2H), 3.64 (br, 1H),3.22 (br, 2H), 3.00 (m, 1H), 2.75 (m, 1H), 2.59 (m, 2H), 2.04 (m, 2H),1.75 (m, 2H), 1.49 (s, 9H), 1.20 (t, 3H), 0.99 (t, 3H)

Preparation 31.(R)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]acetamide

Acetyl chloride (215 μl, 3.02 mmol) and triethylamine (958 μl, 6.88mmol) were added to a solution of(R)-1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-amine (700 mg, 2.75mmol) prepared in Step 1 of Preparation 23 in dichloromethane (5 ml).The reaction mixture was stirred at room temperature for 18 hours andthen diluted with dichloromethane (5 ml). Water was added to thereaction mixture. The separated organic layer was dried on anhydrousmagnesium sulfate, filtered, and then concentrated under reducedpressure. The resulting residue was purified with silica gel columnchromatography (n-hexane/ethyl acetate=5/1) to give 550 mg of the titledcompound as a white solid.

¹H-NMR (400 MHz, CD₃OD) δ 6.54 (s, 1H), 4.06 (m, 2H), 3.79 (br, 1H),3.31 (m, 1H), 3.19 (m, 1H), 2.51 (m, 2H), 2.08 (m, 1H), 1.98 (s, 3H),1.84 (m, 1H), 1.68 (m, 2H), 1.60 (m, 2H), 0.99 (t, 3H)

The synthetic method for the compounds (including the salt thereof) ofthe present invention is described in the following working examples.And also, the compounds of the following working examples and the NMRspectrum data are shown in the subsequent Tables 1-1 to 1-37.

Example 1

A solution of 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine (20mg, 0.08 mmol) prepared in Preparation 1 and piperidine (30 mg, 0.35mmol) in isopropanol (0.5 ml) was stirred at 100° C. overnight. Thereaction mixture was cooled to room temperature and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (n-hexane/ethyl acetate=1/1) to give 11.2 mgof the product as a pale yellow solid.

Examples 2 to 6

The products of Examples 2 to 6 were prepared in accordance with thesame procedures as in Example 1, using4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine prepared inPreparation 1; and morpholine, azepane, 2-methylpiperidine,3-methylpiperidine, or thiomorpholine.

Example 7

A solution of 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine (20mg, 0.08 mmol) prepared in Preparation 1 and 2,5-dimethylpiperazine (30mg, 0.26 mmol) in isopropanol (0.5 ml) was stirred at 100° C. overnight.The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=1/1) andthen dissolved in ethyl acetate (2 ml). The resulting solution wassaturated with hydrogen chloride gas and then filtered to give 5.2 mg ofthe product as a pale yellow solid.

Examples 8 to 12

The products of Examples 8 to 12 were prepared in accordance with thesame procedures as in Example 7, using4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine prepared inPreparation 1; and 1,2,3,6-tetrahydropyridine, decahydroquinoline,decahydroisoquinoline, 4-phenylpiperidine, or morpholine.

Examples 13 to 19

The products of Examples 13 to 19 were prepared in accordance with thesame procedures as in Example 1, using4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine prepared inPreparation 1; and piperazine, 2-ethylpiperidine, 2-piperidineethanol,ethyl piperidin-2-carboxylate, piperidin-4-carboxamide,4-piperidinemethanol, or piperidone.

Examples 20 to 23

The products of Examples 20 to 23 were prepared in accordance with thesame procedures as in Example 1, using4-butyl-6-chloro-N-(4-fluorophenyl)pyrimidin-2-amine prepared inPreparation 2; and piperidine, 2-ethylpiperidine, 2-piperidineethanol,or morpholine.

Example 24

A solution of2-[1-(2-chloro-6-propylpyrimidin-4-yl)-piperidin-2-yl]ethanol (20 mg,0.07 mmol) prepared in Preparation 3 and 4-chloro-3-nitroaniline (20 mg,0.17 mmol) in n-butanol (1 ml) was refluxed under stirring overnight.The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=4/1) togive 6.2 mg of the product as a pale yellow solid.

Example 25

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 24, using2-[1-(2-chloro-6-propylpyrimidin-4-yl)-piperidin-2-yl]ethanol preparedin Preparation 3 and 3-(methylthio)aniline.

Examples 26 to 31

The products of Examples 26 to 31 were prepared in accordance with thesame procedures as in Example 1, using4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine prepared inPreparation 1; and 2,6-dimethylmorpholine,8-azabicyclo[3.2.1]octan-3-ol, 3-acetamidopiperidine,1,3-di-4-piperidylpropane, 3-(benzyloxy)piperidine, or3-oxa-8-azabicyclo[3.2.1]octane.

Example 32

A mixture of 2-chloro-4-(piperidin-1-yl)-6-propylpyrimidine (15 mg, 0.06mmol) prepared in Preparation 5 and 5-aminoindole (20 mg, 0.15 mmol) inn-butanol (1 ml) was refluxed under stirring overnight. The reactionmixture was cooled to room temperature and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (dichloromethane/methanol=50/1) to give 5.3 mg ofthe product as a pale yellow solid.

Examples 33 to 47

The products of Examples 33 to 47 were prepared in accordance with thesame procedures as in Example 32, using2-chloro-4-(piperidin-1-yl)-6-propylpyrimidine prepared in Preparation5; and 3-chloro-4-methylaniline, 6-aminoquinoline,3-(trifluoromethyl)aniline,2-(trifluoromethyl)-1H-benzo[d]imidazol-5-amine, 3-(methylthio)aniline,5-methoxy-2-methylaniline, 5-chloro-2-methylaniline,4-fluoro-3-nitroaniline, 4-methoxyaniline, 3-methoxyaniline,3-chloroaniline, 3-nitroaniline, 4-chloro-3-nitroaniline,3-aminobenzonitrile, or 4-methyl-3-nitroaniline.

Example 48

A solution of 4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine (30mg, 0.13 mmol) prepared in Preparation 10, 1-ethylpiperazine (28.8 mg,0.25 mmol), and diisopropylethylamine (65.7 μl, 0.38 mmol) intetrahydrofuran (1 ml) was stirred at 75° C. for 6 hours. The reactionmixture was cooled to room temperature and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (dichloromethane/methanol=50/1) to give 50.1 mg ofthe product as a white solid.

Examples 49 to 60

The products of Examples 49 to 60 were prepared in accordance with thesame procedures as in Example 48, using4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine prepared inPreparation 10; and 1-(4-methoxyphenyl)piperazine,1-(4-fluorophenyl)piperazine, morpholine, 4-piperidone hydrochloride,piperidine, azetidine hydrochloride, 3-hydroxypiperidine hydrochloride,4-hydroxypiperidine, 2-methylpiperidine, 3-methylpiperidine,cis-3,5-dimethylpiperidine, or hexamethyleneimine.

Example 61

A mixture of 4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine (30mg, 0.13 mmol) prepared in Preparation 10, 2-ethylpiperidine (28.5 mg,0.25 mmol), and diisopropylethylamine (65.7 μl, 0.38 mmol) inisopropanol (1 ml) was reacted in a microwave reactor (300 W) for 2hours. The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=4/1) togive 30.1 mg of the product as a colorless liquid.

Examples 62 to 72

The products of Examples 62 to 72 were prepared in accordance with thesame procedures as in Example 61, using4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine prepared inPreparation 10; and cis-2,6-dimethylpiperidine, 4-phenylpiperidine,piperazine hydrate, 1-methylpiperazine, 2,5-dimethylpiperazine,2,6-dimethylpiperazine, decahydroquinoline, decahydroisoquinoline,1,2,3,6-tetrahydropyridine, 2-piperidineethanol, or2-piperidinemethanol.

Examples 73 and 74

The products of Examples 73 and 74 were prepared in accordance with thesame procedures as in Example 61, usingN-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine prepared inPreparation 6; and decahydroquinoline or 2-piperidineethanol.

Example 75

2-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol(20 mg, 0.05 mmol) prepared in Example 74 was dissolved in ethyl acetate(1 ml) and then hydrogen chloride gas was added thereto. The reactionmixture was stirred at room temperature for 1 hour and then filtered togive 8 mg of the product as a white solid.

Examples 76 to 78

The products of Examples 76 to 78 were prepared in accordance with thesame procedures as in Example 61, usingN-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine prepared inPreparation 6; and piperidine, morpholine, or 2-ethylpiperidine.

Example 79

A solution of 4-(2-chloro-6-propylpyrimidin-4-yl)morpholine (550 mg,2.28 mmol) prepared in Preparation 11 and 6-aminoindole (300 mg, 2.28mmol) in n-butanol (2.3 ml) was refluxed under stirring for 1 hour andthen cooled to room temperature. Ethyl acetate was added to the reactionmixture. The resulting precipitate was collected by filtration and thenwashed with ethyl acetate to give 760 mg of the product as a whitesolid.

Examples 80 and 81

The products of Examples 80 and 81 were prepared in accordance with thesame procedures as in Example 61, using3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile prepared inPreparation 4; and (R)-3-ethylmorpholine or (R)-tert-butyl 3-methylpiperazine-1-carboxylate.

Example 82

Hydrogen chloride gas was added at 0° C. for 1 minute to a solution of(R)-tert-butyl4-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]-3-methylpiperazin-1-carboxylate(20 mg, 0.05 mmol) prepared in Example 81 in ethyl acetate (3 ml). Thereaction mixture was stirred at room temperature for 2 hours and thenfiltered to give 19.3 mg of the product as a white solid.

Example 83

A solution of 4-(2-chloro-6-propylpyrimidin-4-yl)morpholine (20 mg, 0.08mmol) prepared in Preparation 11 and 3-nitroaniline (12.6 mg, 0.09 mmol)in n-butanol (0.5 ml) was reacted in a microwave reactor (450 W) for 40minutes. The reaction mixture was cooled to room temperature. Theresulting precipitate was collected by filtration and then washed withethyl acetate to give 22.1 mg of the product as a yellow solid.

Examples 84 to 94

The products of Examples 84 to 94 were prepared in accordance with thesame procedures as in Example 79, using4-(2-chloro-6-propylpyrimidin-4-yl)morpholine prepared in Preparation11; and 4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline,3-methoxyaniline, 4-methoxyaniline, 3-(methylthio)aniline,3-chloroaniline, 2-chloro-4-aminotoluene, 3-(trifluoromethyl)aniline,5-aminoindole, 5-amino-2-(trifluoromethyl)benzimidazole, or6-aminoquinoline.

Example 95

A solution of 4-(2-chloro-6-propylpyrimidin-4-yl)morpholine (20 mg, 0.08mmol) prepared in Preparation 11 and 3-aminobenzonitrile (12.6 mg, 0.09mmol) in n-butanol (0.5 ml) was reacted in a microwave reactor (450 W)for 40 minutes. The reaction mixture was cooled to room temperature andthen concentrated under reduced pressure. The resulting residue waspurified with silica gel column chromatography(dichloromethane/methanol=50/1) to give 20.1 mg of the product as awhite solid.

Example 96

A mixture of 4-(2-chloro-6-propylpyrimidin-4-yl)morpholine (25 mg, 0.1mmol) prepared in Preparation 11, 5-methoxy-2-methylaniline (14.1 mg,0.103 mmol), palladium acetate (1.2 mg, 0.005 mmol),4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (3 mg, 0.005 mmol),cesium carbonate (67.0 mg, 0.21 mmol), and 1,4-dioxane (0.5 ml) wasreacted in a microwave reactor (600 W) for 30 minutes. The reactionmixture was cooled to room temperature and then water was added thereto.The reaction mixture was extracted with dichloromethane. The resultingorganic layer was dried on anhydrous sodium sulfate and then filtered.The filtrate was concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(dichloromethane/methanol=50/1) to give 19 mg of the product as a whitesolid.

Examples 97 and 98

The products of Examples 97 and 98 were prepared in accordance with thesame procedures as in Example 96, using4-(2-chloro-6-propylpyrimidin-4-yl)morpholine prepared in Preparation11; and 5-chloro-2-methylaniline or 3-aminoquinoline.

Examples 99 to 111

The products of Examples 99 to 111 were prepared in accordance with thesame procedures as in Example 95, using2-chloro-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidine prepared inPreparation 14; and 3-nitroaniline, 4-fluoro-3-nitroaniline,4-chloro-3-nitroaniline, 3-anisidine, 4-anisidine,3-(methylthio)aniline, 3-chloroaniline, 2-chloro-4-aminotoluene,3-(trifluoromethyl)aniline, 5-aminoindole,5-amino-2-(trifluoromethyl)benzimidazole, 6-aminoquinoline, or3-aminobenzonitrile.

Examples 112 to 114

The products of Examples 112 to 114 were prepared in accordance with thesame procedures as in Example 96, using2-chloro-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidine prepared inPreparation 14; and 5-methoxy-2-methylaniline, 5-chloro-2-methylaniline,or 3-aminoquinoline.

Example 115

N-(4-chloro-3-nitrophenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine(20 mg, 0.05 mmol) prepared in Example 101 was dissolved in ethylacetate (1 ml) and hydrogen chloride gas was added thereto. The reactionmixture was stirred at room temperature for 1 hour and then filtered togive 15.5 mg of the product as a white solid.

Example 116

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 115, using3-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrileprepared in Example 111.

Examples 117 to 130

The products of Examples 117 to 130 were prepared in accordance with thesame procedures as in Example 95, using (R)-tert-butyl4-(2-chloro-6-propylpyrimidin-4-yl)-3-methylpiperazin-1-carboxylateprepared in Preparation 15; and 4-chloro-3-nitroaniline, 6-aminoindole,3-(trifluoromethyl)aniline, 3-nitroaniline, 4-fluoro-3-nitroaniline,4-methyl-3-nitroaniline, 4-fluorobenzene-1,3-diamine,2-(trifluoromethyl)benzene-1,4-diamine, 5-amino-2-fluorobenzonitrile,5-amino-2-methylbenzonitrile, 2,5-diaminobenzonitrile,2-nitrobenzene-1,4-diamine, 3,5-diaminobenzonitrile, or3-aminobenzamide.

Example 131

A mixture of2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanol (35 mg,0.12 mmol) prepared in Preparation 3,3-aminobenzonitrile (18 mg, 0.15mmol), and n-butanol (1 ml) was refluxed under stirring overnight. Thereaction mixture was cooled to room temperature and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (dichloromethane/methanol=20/1) to give 43.7mg of the product as a pale yellow solid.

Example 132 <Step 1>2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol

The titled compound (150 mg) in the form of white solid was prepared inaccordance with the same procedures as in Example 131, using2-[1-(2-chloro-6-propylpyrimidin-4-yl)-piperidin-2-yl]ethanol preparedin Preparation 3 and 4-chloro-3-nitroaniline.

<Step 2>2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanolhydrochloride

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 115, using2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanolprepared in Step 1.

Example 133

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 132, using2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanol and3-(methylthio)aniline prepared in Preparation 3.

Examples 134 to 147

The products of Examples 134 to 147 were prepared in accordance with thesame procedures as in Example 131, using2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanol prepared inPreparation 3; and 1-ethyl-1H-indol-6-amine prepared in Preparation 21,5-aminoindole, 5-amino-2-(trifluoromethyl)benzimidazole,4-methoxyaniline, 3-methoxyaniline, 5-methoxy-2-methylaniline,4-amino-2-chlorotoluene, 3-nitroaniline, 4-fluoro-3-nitroaniline,2,3-dimethylbenzofuran-5-amine prepared in Preparation 22,6-aminoquinoline, 3-chloroaniline, 7-amino-4-methyl-2H-chromen-2-one, or3-(trifluoromethyl)aniline.

Example 148

3-Aminoquinoline (22 mg, 0.15 mmol) was added to a mixture of2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanol (35 mg,0.12 mmol) prepared in Preparation 3, palladium acetate (0.5 mg, 2 mol%), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (2.1 mg, 3 mol %),cesium carbonate (78 mg, 0.24 mmol), and anhydrous 1,4-dioxane (1 ml).The reaction mixture was stirred in a microwave reactor (600 W) for 1hour and then cooled to room temperature. The reaction mixture wassuspended in dichloromethane and then filtered through a celite pad. Theresulting filtrate was concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(dichloromethane/methanol=20/1) to give 45.5 mg of the product as a paleyellow solid.

Example 149

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 115, using3-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrileprepared in Example 131.

Examples 150 to 152

The products of Examples 150 to 152 were prepared in accordance with thesame procedures as in Example 132, using (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-ylcarbamate prepared inPreparation 20; and 5-amino-2-methylbenzonitrile, 3-nitroaniline, or3-aminobenzonitrile.

Example 153

(R)-(−)-3-Aminopiperidine dihydrochloride (18 mg, 0.1 mmol), sodiumbicarbonate (42 mg, 0.5 mmol), and molecular sieve (1 g) were added to asolution of5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile (30 mg,0.1 mmol) prepared in Preparation 7 in ethanol. The reaction mixture wasstirred at 130° C. overnight. The reaction mixture was cooled to roomtemperature and then filtered to discard insoluble materials. Thefiltrate was concentrated under reduced pressure. The resulting residuewas purified with silica gel column chromatography(methanol/dichloromethane=1/10) to give 19.2 mg of the product as a paleyellow solid.

Example 154 <Step 1>(S)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyridin-2-ylamino]-2-methylbenzonitrile

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 153, using5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile preparedin Preparation 7 and (S)-(−)-3-aminopiperidine.

<Step 2>(S)-5-{4-[3-(butylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile

Butyraldehyde (6.5 mg, 0.09 mmol) was added to a solution of(S)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyridin-2-ylamino]-2-methylbenzonitrile(24.5 mg, 0.07 mmol) prepared in Step 1 in methanol (1 ml). The reactionmixture was stirred at room temperature for 30 minutes and then sodiumcyanoborohydride (6.84 mg, 0.11 mmol) was added thereto. The reactionmixture was stirred at room temperature overnight and then a 1Nhydrochloric acid solution was added thereto. The reaction mixture wasstirred for 30 minutes, neutralized with a 1N sodium hydroxide solution,and then extracted with ethyl acetate. The organic layer was dried onanhydrous magnesium sulfate, filtered, and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (ethyl acetate/methanol=20/1) to give 10.2 mg ofthe product as a pale yellow solid.

Examples 155 to 164

The products of Examples 155 to 164 were prepared in accordance with thesame procedures as in Step 2 of Example 154, using(S)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyridin-2-ylamino]-2-methylbenzonitrileprepared in Step 1 of Example 154; and pentanal, isobutylaldehyde,3-methylbutanal, pivaldehyde, pyrrole-2-carboxaldehyde,2-thiophenecarboxaldehyde, 4,5-dimethyl-2-furaldehyde,3-(methylthio)propionaldehyde, cyclopropane carboxaldehyde, or4-hydroxybenzaldehyde.

Examples 165 and 166

The products of Examples 165 and 166 in the form of pale yellow solidwere prepared in accordance with the same procedures as in Step 2 ofExample 154, using(S)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyridin-2-ylamino]-2-methylbenzonitrileprepared in Step 1 of Example 154; and acetaldehyde or cyclopropanecarboxaldehyde.

Example 167

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Step 2 of Example 154, using(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyridin-2-ylamino]-2-methylbenzonitrileprepared in Example 153 and cyclopropane carboxaldehyde.

Example 168

A solution of 4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine (20mg, 0.08 mmol) prepared in Preparation 9 and piperidine (9.4 μl, 0.10mmol) in isopropanol (0.5 ml) was stirred at 100° C. overnight. Thereaction mixture was cooled to room temperature and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (dichloromethane/methanol=40/1) to give 6.2 mgof the product as a pale yellow oil.

Examples 169 to 172

The products of Examples 169 to 172 were prepared in accordance with thesame procedures as in Example 168, using4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine prepared inPreparation 9; and decahydroquinoline, 2-ethylpiperidine,2-piperidineethanol, or morpholine.

Example 173

The product was prepared in accordance with the same procedures as inExample 115, usingN-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine preparedin Example 76.

Examples 174 to 179

The products of Examples 174 to 179 were prepared in accordance with thesame procedures as in Example 131, using2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanol prepared inPreparation 3; and 4-methyl-3-nitroaniline,2-(trifluoromethyl)-1,4-phenylenediamine, 2-nitro-1,4-phenylenediamine,5-amino-2-methylbenzonitrile, 5-amino-2-fluorobenzonitrile, or2,5-diaminobenzonitrile prepared in Preparation 16.

Example 180

A mixture of2-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol(17 mg, 0.04 mmol) prepared in Example 174, palladium/charcoal (10 mg,10 wt %), and methanol (2 ml) was stirred under hydrogen atmosphere atroom temperature for 1 hour. The reaction mixture was filtered throughcelite pad. The filtrate was concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(dichloromethane/methanol=70/1) to give 4.2 mg of the product as a paleyellow solid.

Example 181

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 180, using2-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanolprepared in Example 142.

Example 182

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 180, using2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanolprepared in Example 24.

Example 183 <Step 1>1-(6-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}indolin-1-yl)ethanone

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as in Example 131, using2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanol prepared inPreparation 3 and 1-acetyl-6-aminoindoline. The product was used in thesubsequent step without further purification. (Yield: 77%).

<Step 2>2-{1-[2-(indolin-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol

A mixture of1-(6-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}indolin-1-yl)ethanone(35.8 mg, 0.12 mmol) prepared in Step 1 and a 10% hydrochloric acidsolution (1.5 ml) was refluxed under stirring for 2 hours. The reactionmixture was cooled to room temperature, controlled to pH 5 with a 2Nsodium hydroxide solution, and then extracted with dichloromethane. Theresulting organic layer was dried on anhydrous sodium sulfate and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (dichloromethane/methanol=30/1) togive 11.4 mg of the titled compound as a colorless solid.

Examples 184 and 185

The products of Examples 184 and 185 were prepared in accordance withthe same procedures as in Example 131, using(S)-2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanolprepared in Preparation 17; and 4-chloro-3-nitroaniline or2-nitro-1,4-phenylenediamine.

Example 186

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 131, using(R)-2-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-2-yl]ethanolprepared in Preparation 18 and 2-nitro-1,4-phenylenediamine.

Example 187

A solution of 1-(2-chloro-6-propylpyrimidin-4-yl)decahydroquinoline(25.6 mg, 0.09 mmol) prepared in Preparation 19 and 3-aminobenzonitrile(12.3 mg, 0.10 mmol) in n-butanol (1 ml) was stirred at 120° C.overnight. The reaction mixture was concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(dichloromethane/methanol=70/1) to give 10.8 mg of the product as a paleyellow oil.

Examples 188 to 202

The products of Examples 188 to 202 were prepared in accordance with thesame procedures as in Example 187, using1-(2-chloro-6-propylpyrimidin-4-yl)decahydroquinoline prepared inPreparation 19; and 3-nitroaniline, 4-fluoro-3-nitroaniline,4-chloro-3-nitroaniline, 3-methoxyaniline, 5-methoxy-2-methylaniline,4-methoxyaniline, 3-(trifluoromethyl)aniline, 3-chloroaniline,5-chloro-2-methylaniline, 2-chloro-4-aminotoluene,3-(methylthio)aniline, 5-aminoindole,5-amino-2-(trifluoromethyl)benzimidazole, 6-aminoquinoline, or7-amino-4-methyl-2H-chromen-2-one.

Example 203

A mixture of 1-(2-chloro-6-propylpyrimidin-4-yl)decahydroquinoline (25mg, 0.09 mmol) prepared in Preparation 19, palladium acetate (0.38 mg,0.002 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.48 mg,0.003 mmol), cesium carbonate (55 mg, 0.17 mmol), 3-aminoquinoline (12.3mg, 0.09 mmol), and 1,4-dioxane (0.4 ml) was stirred in a microwavereactor (600 W) for 2 hours. The reaction mixture was concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (dichloromethane/methanol=30/1) to give 2 mg ofthe product as a white solid.

Example 204

The product in the form of pale red solid was prepared in accordancewith the same procedures as in Example 115, usingN-[4-(octahydroquinoline-1(2H)-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amineprepared in Example 73.

Examples 205 to 219

The products of Examples 205 to 219 were prepared in accordance with thesame procedures as in Step 2 of Example 154, using(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrileprepared in Example 153; and acetaldehyde, propionaldehyde,butyraldehyde, valeraldehyde, isobutyraldehyde, isovaleraldehyde,pivaldehyde, acetone, pyrrole-2-carboxaldehyde,2-thiophenecarboxaldehyde, 4,5-dimethyl-2-furaldehyde,3-(methylthio)propionaldehyde, cyclopropane carboxaldehyde, cyclopentanecarboxaldehyde, or 4-hydroxybenzaldehyde.

Example 220

Acetyl chloride (31 μl, 0.44 mmol) and triethylamine (100 μl, 0.73 mmol)were added to a solution of(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile(100 mg, 0.29 mmol) prepared in Example 153 in dichloromethane (2 ml).The reaction mixture was stirred at room temperature for 18 hours andthen diluted with dichloromethane (5 ml). Water was added to thereaction mixture. The separated organic layer was dried on anhydrousmagnesium sulfate, filtered, and then concentrated under reducedpressure. The resulting residue was purified with silica gel columnchromatography (n-hexane/ethyl acetate=1/1) and then dissolved in ethylacetate (2 ml). The resulting solution was saturated with hydrogenchloride gas and then filtered to give 56 mg of the product as a whitesolid.

Example 221

(R)-(−)-3-aminopiperidine dihydrochloride (190 mg, 1.10 mmol), sodiumbicarbonate (461.1 mg, 5.50 mmol), and molecular sieve (1 g) were addedto a solution of 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile(299.4 mg, 1.10 mmol) prepared in Preparation 4 in ethanol (5.5 ml). Thereaction mixture was stirred at 130° C. overnight. The reaction mixturewas cooled to room temperature and then filtered to discard insolublematerials. The filtrate was concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(methanol/dichloromethane=1/10) to give 334 mg of the product as a paleyellow oil. The product (84 mg) was dissolved in ethyl acetate (2 ml).The resulting solution was saturated with hydrogen chloride gas and thenfiltered to give 90.7 mg of the product as a white solid.

Example 222

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 221, using5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile preparedin Preparation 8 and (R)-(−)-3-aminopiperidine dihydrochloride.

Example 223

(R)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile(120 mg, 0.36 mmol) [obtained by treating(R)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Example 221 with an aqueous saturatedsolution of sodium bicarbonate] was dissolved in methanol (5 ml).Propionaldehyde (25.6 μl, 0.36 mmol) was added to the solution, whichwas then stirred at room temperature for 1 hour. Sodium cyanoborohydride(151 mg, 0.72 mmol) was added to the reaction mixture, which was thenstirred at room temperature overnight. A 1N hydrochloric acid solutionwas added to the reaction mixture, which was then stirred at 30 minutes.The reaction mixture was neutralized with a 1N sodium hydroxide solutionand then extracted with ethyl acetate. The organic layer was dried onanhydrous magnesium sulfate, filtered, and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (ethyl acetate/methanol=10/1) to give 13.6 mg ofthe product as a colorless oil.

Example 224

The product in the form of colorless oil was prepared in accordance withthe same procedures as in Example 223, using cyclopropane carboxaldehydeand(R)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile[obtained by treating(R)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Example 221 with an aqueous saturatedsolution of sodium bicarbonate]. The resulting product was dissolved inethyl acetate (2 ml). The solution was saturated with hydrogen chloridegas and then filtered to give the product as a white solid.

Example 225

The product in the form of colorless oil was prepared in accordance withthe same procedures as in Example 223, using propionaldehyde and(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile[obtained by treating(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitriledihydrochloride prepared in Example 222 with an aqueous saturatedsolution of sodium bicarbonate].

Example 226

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 224, using cyclopropane carboxaldehydeand(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile[obtained by treating(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitriledihydrochloride prepared in Example 222 with an aqueous saturatedsolution of sodium bicarbonate].

Example 227

A solution of (R)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl(cyclopropylmethyl)carbamate(36.4 mg, 0.09 mmol) prepared in Preparation 23 and4-fluorobenzene-1,3-diamine (13.5 mg, 0.11 mmol) in n-butanol (0.5 ml)was stirred at 120° C. for 2 days. The reaction mixture was concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (dichloromethane/methanol=10/1) to give 9.9 mgof the product as a pale yellow oil.

Examples 228 to 231

The products of Examples 228 to 231 were prepared in accordance with thesame procedures as in Example 227, using (R)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl(cyclopropylethyl)carbamateprepared in Preparation 23; and 2-nitrobenzene-1,4-diamine,3,5-diaminobenzonitrile, 2-(trifluoromethyl)benzene-1,4-diamine, or5-(trifluoromethyl)benzene-1,3-diamine.

Example 232

A solution of(R)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]acetamide (165mg, 0.53 mmol) prepared in Preparation 24 and2-nitro-1,4-phenylenediamine (90 mg, 0.58 mmol) in n-butanol (2 ml) wasstirred at 130° C. for 2 hours. The reaction mixture was cooled to roomtemperature and then dichloromethane (3 ml) was added thereto. Thereaction mixture was stirred at room temperature for 1 hour and thenfiltered. The resulting solid was dried in vacuo to give 120 mg of theproduct as a pale yellow solid.

Examples 233 to 243

The products of Examples 233 to 243 were prepared in accordance with thesame procedures as in Example 232, using(R)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]acetamideprepared in Preparation 24; and 4-methyl-3-nitroaniline,4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline,3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine,2-(trifluoromethyl)benzene-1,4-diamine,4-fluoro-3-trifluoromethylphenylamine, 5-amino-2-fluorobenzonitrile,4-fluoro-1,3-phenylenediamine, 4-chloro-1,3-phenylenediamine, or2,5-diaminobenzonitrile prepared in Preparation 16.

Example 244

A mixture of(R)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]-2-hydroxyacetamide(22 mg, 0.07 mmol) prepared in Preparation 25 and5-amino-2-methylbenzonitrile (10.6 mg, 0.08 mmol) in n-butanol (0.5 ml)was stirred in a microwave reactor (600 W) for 1 hour. The reactionmixture was concentrated under reduced pressure. The resulting residuewas purified with silica gel column chromatography(dichloromethane/methanol=20/1) to give 7.5 mg of the product as ayellow oil.

Examples 245 to 254

The products of Examples 245 to 254 were prepared in accordance with thesame procedures as in Example 244, using(R)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]-2-hydroxyacetamideprepared in Preparation 25; and 3-aminobenzonitrile,5-amino-2-fluorobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine,2-(trifluoromethyl)benzene-1,4-diamine,4-fluoro-3-trifluoromethylphenylamine, 4-fluoro-1,3-phenylenediamine,4-chloro-1,3-phenylenediamine, 2,4-diaminotoluene,2-chloro-4-aminotoluene, or 4-methyl-3-(trifluoromethyl)aniline.

Example 255

A mixture of(R)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]-2-hydroxyacetamide(20 mg, 0.06 mmol) prepared in Preparation 25 and3,5-diaminobenzonitrile (10.2 mg, 0.08 mmol) in n-butanol (0.5 ml) wasstirred in a microwave reactor (600 W) for 1 hour. The reaction mixturewas cooled to room temperature and then ethyl acetate (2 ml) was addedthereto. The reaction mixture was stirred at room temperature for 1 hourand then filtered. The resulting solid was dried in vacuo to give 3.9 mgof the product as a pale yellow solid.

Example 256

A solution of (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]carbamate (82 mg,0.23 mmol) prepared in Preparation 26 and5-(trifluoromethyl)benzene-1,3-diamine (44 mg, 0.25 mmol) in n-butanol(1 ml) was stirred at 130° C. for 3 hours. The reaction mixture wascooled to room temperature and then concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(dichloromethane/methanol=20/1) and then dissolved in ethylacetate/methanol (1 ml/1 ml). The resulting solution was saturated withhydrogen chloride gas and then filtered to give 55.5 mg of the productas a white solid.

Examples 257 to 266

The products of Examples 257 to 266 were prepared in accordance with thesame procedures as in Example 256, using (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]carbamate prepared inPreparation 26; and 2-(trifluoromethyl)benzene-1,4-diamine,3-fluoro-4-methylaniline, 4-fluoro-1,3-phenylenediamine,3,5-diaminobenzonitrile, 2,5-diaminobenzonitrile prepared in Preparation16, 4-chloro-1,3-phenylenediamine, 4-methyl-3-(trifluoromethyl)aniline,6-aminoindole, 4-methyl-3-nitroaniline, or 2-nitrobenzene-1,4-diamine.

Example 267

(R)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile(20 mg, 0.05 mmol) prepared in Example 217 was dissolved in ethylacetate (1 ml), and then hydrogen chloride gas was added thereto. Thereaction mixture was stirred at room temperature for 1 hour and thenfiltered to give 14 mg of the product as a white solid.

Example 268

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 220, using(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitriledihydrochloride prepared in Example 222.

Example 269

The product in the form of white solid was prepared in accordance withthe same procedures as in Step 2 of Example 154, using(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrileprepared in Example 153 and acetaldehyde.

Example 270

The reactions were performed in accordance with the same procedures asin Step 2 of Example 154, using(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitriledihydrochloride prepared in Example 222 and acetaldehyde. The resultingintermediate product was treated with hydrogen chloride gas to give theproduct as a white solid

Example 271

The product in the form of white solid was prepared in accordance withthe same procedures as in Step 2 of Example 154, using(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitriledihydrochloride prepared in Example 222 and acetaldehyde.

Example 272 <Step 1>(R)-3-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 153, using3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile prepared inPreparation 12.

<Step 2>(R)—N-{1-[6-butyl-2-(3-cyanophenylamino)-pyrimidin-4-yl]-piperidin-3-yl}-acetamidehydrochloride

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 220, using(R)-3-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrileprepared in Step 1.

Example 273

A mixture of(R)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]acetamide (60mg, 0.2 mmol) prepared in Preparation 31 and 3-aminobenzonitrile (28 mg,0.24 mmol) in n-butanol (1 ml) was refluxed under stirring overnight.The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=1/1) andthen dissolved in ethyl acetate. Hydrogen chloride gas was added to thesolution and the resulting precipitate was collected by filtration togive 68.8 mg of the product as a pale yellow solid.

Examples 274 to 279

The products of Examples 274 to 279 were prepared in accordance with thesame procedures as in Example 273, using(R)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl]acetamideprepared in Preparation 31; and 3,5-diaminobenzonitrile,2-nitro-1,4-phenylenediamine, 4-fluoro-1,3-diaminobenzene,5-amino-2-fluorobenzotrifluoride,5-(trifluoromethyl)-1,3-phenylenediamine or2-(trifluoromethyl)-1,4-phenylenediamine.

Example 280

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 267, using(R)-5-{4-[3-(ethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrileprepared in Example 205.

Example 281

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 267, using(R)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrileprepared in Example 271.

Example 282

A solution of (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](methyl)carbamate (50mg, 0.14 mmol) prepared in Preparation 28 and5-amino-2-fluorobenzonitrile (23 mg, 0.17 mmol) in n-butanol (1 ml) wasrefluxed under stirring overnight. The reaction mixture was cooled toroom temperature and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1→dichloromethane/methanol=10/1) and thendissolved in methanol. Hydrogen chloride gas was added to the solution.The reaction mixture was stirred at room temperature for 5 hours andthen filtered to give 23 mg of the product as a pale yellow solid.

Examples 283 to 287

The products of Examples 283 to 287 were prepared in accordance with thesame procedures as in Example 282, using (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](methyl)carbamateprepared in Preparation 28; and 5-amino-2-methylbenzonitrile,5-(trifluoromethyl)-1,3-phenylenediamine,2-(trifluoromethyl)-1,4-phenylenediamine, 3,5-diaminobenzonitrile, or4-fluoro-3-(trifluoromethyl)aniline.

Example 288

A solution of (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](ethyl)carbamate (85mg, 0.22 mmol) prepared in Preparation 30 and2-nitro-1,4-phenylenediamine (41 mg, 0.27 mmol) in n-butanol (1 ml) wasrefluxed under stirring overnight. The reaction mixture was cooled toroom temperature and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1→dichloromethane/methanol=10/1) and thendissolved in methanol. Hydrogen chloride gas was added to the solution.The reaction mixture was stirred at room temperature for 5 hours andthen filtered to give 104 mg of the product as a pale red solid.

Examples 289 to 292

The products of Examples 289 to 292 were prepared in accordance with thesame procedures as in Example 288, using (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](ethyl)carbamateprepared in Preparation 30; and 4-fluoro-1,3-diaminobenzene,5-(trifluoromethyl)-1,3-phenylenediamine,2-(trifluoromethyl)-1,4-phenylenediamine or 3,5-diaminobenzonitrile.

Example 293

The product was prepared in accordance with the same procedures as inExample 153, using5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile prepared inPreparation 13 and (R)-(−)-3-aminopiperidine dihydrochloride.

Example 294 <Step 1>5-[(4-butyl-6-chloropyrimidin-2-yl)amino]-2-fluorobenzonitrile

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Steps 2 and 3 of Preparation12, using 6-butyl-2-(methylthio)pyrimidin-4(3H)-one prepared in Step 1of Preparation 12 and 5-amino-2-fluorobenzonitrile.

<Step 2>(R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-fluorobenzonitrile

The titled compound was prepared in accordance with the same proceduresas in Example 153, using5-[(4-butyl-6-chloropyrimidin-2-yl)amino]-2-fluorobenzonitrile preparedin Step 1 and (R)-(−)-3-aminopiperidine dihydrochloride.

Example 295

The product was prepared in accordance with the same procedures as inExample 220, using(R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitrileprepared in Example 293.

Example 296 <Step 1>(S)-5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}-2-methylbenzonitrile

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as in Example 153, using5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile preparedin Preparation 7 and (S)-(+)-3-aminopiperidine dihydrochloride.

<Step 2>(S)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Step 2 of Example 154, using(S)-5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}-2-methylbenzonitrileprepared in Step 1 and acetaldehyde.

<Step 3>(S)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 267, using(S)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrileprepared in Step 2.

Example 297 <Step 1>5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}-2-methylbenzonitrile

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as in Example 153, using5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile preparedin Preparation 7 and 3-aminopiperidine dihydrochloride.

<Step 2>5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Step 2 of Example 154, using5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}-2-methylbenzonitrileprepared in Step 1 and acetaldehyde.

<Step 3>5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 267, using5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrileprepared in Step 2.

Example 298 <Step 1>N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as in Example 153, using5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile prepared inPreparation 13 and 3-acetamidopiperidine.

<Step 2>N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamidehydrochloride

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Example 267, usingN-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamideprepared in Step 1.

Examples 299 to 305

The products of Examples 299 to 305 were prepared in accordance with thesame procedures as in Step 2 of Example 154, using(R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitrileprepared in Example 293; and acetaldehyde, butyraldehyde, valeraldehyde,isobutyraldehyde, isovaleraldehyde, pivaldehyde or3-(methylthio)propionaldehyde.

Examples 306 to 310

The products of Examples 306 to 310 were prepared in accordance with thesame procedures as in Example 282, using (R)-tert-butyl[1-(2-chloro-6-propylpyrimidin-4-yl)piperidin-3-yl](methyl)carbamateprepared in Preparation 28; and 4-fluoro-1,3-diaminobenzene,4-chloro-1,3-diaminobenzene, 2,5-diaminobenzonitrile prepared inPreparation 16, 3-methoxy-4-methylaniline or 2,4-diaminotoluene.

Example 311

A solution of (R)-tert-butyl[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl](methyl)carbamate (40mg, 0.1 mmol) prepared in Preparation 29, 5-amino-2-methylbenzonitrile(15.9 mg, 0.12 mmol) in n-butanol (1 ml) was refluxed under stirring for2 hours. The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethylacetate=1/1→dichloromethane/methanol=10/1) and then dissolved inmethanol. Hydrogen chloride gas was added to the solution. The reactionmixture was stirred at room temperature for 5 hours and then filtered togive 33.5 mg of the product as a pale yellow solid.

Examples 312 to 320

The products of Examples 312 to 320 were prepared in accordance with thesame procedures as in Example 311, using (R)-tert-butyl[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl](methyl)carbamateprepared in Preparation 29; and 5-amino-2-fluorobenzonitrile,5-(trifluoromethyl)-1,3-phenylenediamine,2-(trifluoromethyl)-1,4-phenylenediamine, 3,5-diaminobenzonitrile,2,5-diaminobenzonitrile prepared in Preparation 16,4-fluoro-1,3-diaminobenzene, 3-methoxy-4-methylaniline,2,4-diaminotoluene, or 5-amino-2-fluorobenzotrifluoride.

Examples 321 to 326

The products of Examples 321 to 326 were prepared in accordance with thesame procedures as in Example 282, using (R)-tert-butyl(1-[2-chloro-6-propylpyrimidin-4-yl]piperidin-3-yl)(methyl)carbamateprepared in Preparation 28; and 2-nitro-1,4-phenylenediamine,3,4-dimethylaniline, 3-fluoro-4-methylaniline,4-methyl-3-(trifluoromethyl)aniline, 2,4-diaminoanisole or6-aminoindazole.

Example 327

Palladium/charcoal (25 mg, 10 wt %) was added to a solution of(R)—N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diaminedihydrochloride (20 mg, 0.04 mmol) prepared in Example 321 in methanol(2 ml). The reaction mixture was stirred at room temperature underhydrogen atmosphere (30 bar) for 3 hours and then filtered through acelite pad. The resulting filtrate was concentrated under reducedpressure. The resulting residue was purified with silica gel columnchromatography (dichloromethane/methanol=10/1) to give 3.5 mg of theproduct as a pale yellow solid.

Examples 328 to 334

The products of Examples 328 to 334 were prepared in accordance with thesame procedures as in Example 282, using (R)-tert-butyl[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl](methyl)carbamateprepared in Preparation 29; and 2-nitro-1,4-phenylenediamine,3-aminobenzonitrile, 3,4-dimethylaniline, 3-fluoro-4-methylaniline,4-methyl-3-(trifluoromethyl)aniline, 2,4-diaminoanisole or6-aminoindazole.

Example 335

The product was prepared in accordance with the same procedures as inExample 327, using(R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-3-nitrobenzene-1,4-diaminedihydrochloride prepared in Example 328.

Example 336

A solution of (R)-tert-butyl[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]carbamate (40 mg, 0.11mmol) prepared in Preparation 27 and 3-nitroaniline (16.6 mg, 0.12 mmol)in n-butanol (1 ml) was refluxed under stirring for 2 hours and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethylacetate=1/1→dichloromethane/methanol=10/1) and then dissolved inmethanol (2 ml). The resulting solution was saturated with hydrogenchloride gas. The reaction mixture was stirred at room temperature for 5hours and then filtered. The filtrate was concentrated under reducedpressure. Ethyl acetate (2 ml) was added to the resulting residue, whichwas then stirred. The reaction mixture was filtered to give 35 mg of theproduct as a white solid.

Examples 337 to 353

The products of Examples 337 to 353 were prepared in accordance with thesame procedures as in Example 336, using (R)-tert-butyl[1-(6-butyl-2-chloropyrimidin-4-yl)piperidin-3-yl]carbamate prepared inPreparation 27; and 2-nitro-1,4-phenylenediamine,4-fluoro-3-nitroaniline, 4-methyl-3-nitroaniline,2-(trifluoromethyl)-1,4-phenylenediamine,5-(trifluoromethyl)-1,3-phenylenediamine, 3,5-diaminobenzonitrile,4-methyl-3-(trifluoromethyl)aniline, 3-fluoro-4-methylaniline,3-methoxy-4-methylaniline, 2,4-diaminotoluene, 3,4-dimethylaniline,5-amino-2-fluorobenzotrifluoride, 4-fluoro-1,3-diaminobenzene,2,5-diaminobenzonitrile prepared in Preparation 16, 3-aminobenzonitrile,1,4-phenylenediamine, or 4-chloro-3-nitroaniline.

Example 354

The product was prepared in accordance with the same procedures as inExample 327, using(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-3-nitrobenzene-1,4-diaminedihydrochloride prepared in Example 337.

The compounds of Examples 1 to 354 and the NMR spectrum data thereof areshown in Tables 1-1 to 1-37 below.

TABLE 1-1 Example Compound NMR Spectrum 1N-(4-fluorophenyl)-4-(piperidin- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m,2H), 1-yl)-6-propylpyrimidin-2-amine 6.98(t, 2H), 5.90(s, 1H), 3.58(t,4H), 2.45(t, 2H), 1.80-1.50(m, 6H), 0.98(t, 3H) 2N-(4-fluorophenyl)-4-morpholino- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m,2H), 6-propylpyrimidin-2-amine 6.99(t, 2H), 5.89(s, 1H), 3.78(t, 4H),3.58(t, 4H), 2.48(t, 2H), 1.72(q, 2H), 0.98(t, 3H) 34-(azepan-1-yl)-N-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H),fluorophenyl)-6-propylpyrimidin- 6.96(t, 2H), 5.80(s, 1H), 3.90-3.30(m,4H), 2.45(t, 2-amine 2H), 1.90-1.65(m, 6H), 1.60-1.50(m, 4H), 0.98(t,3H) 4 N-(4-fluorophenyl)-4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m,2H), methylpiperidin-1-yl)-6- 6.97(t, 2H), 5.88(s, 1H), 4.70-4.60(m,1H), 4.21(d, propylpyrimidin-2-amine 1H), 2.93(t, 1H), 2.45(t, 2H),1.80-1.60(m, 7H), 1.19(d, 3H), 0.98(t, 3H) 5 N-(4-fluorophenyl)-4-(3-¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), methylpiperidin-1-yl)-6-6.97(t, 2H), 5.90(s, 1H), 4.30-4.10(m, 2H), 2.85(t,propylpyrimidin-2-amine 1H), 2.52(t, 1H), 2.45(t, 2H), 1.85(d, 1H),1.80- 1.60(m, 4H), 1.60-1.45(m, 1H), 1.20(q, 1H), 1.00- 0.90(m, 6H) 6N-(4-fluorophenyl)-4-propyl-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.55-7.45(m,2H), thiomorpholinopyrimidin-2-amine 6.98(t, 2H), 5.87(s, 1H),4.00-3.90(m, 4H), 2.70- 2.60(m, 4H), 2.47(t, 2H), 1.72(q, 2H), 0.97(t,3H) 7 4-(2,5-dimethylpiperazin-1-yl)-N- ¹H-NMR(400 MHz, CD₃OD) δ7.60-7.50(m, 2H), (4-fluorophenyl)-6- 7.18(t, 2H), 6.59(d, 1H),3.50-3.30(m, 2H), 3.20- propylpyrimidin-2-amine 3.00(m, 2H),2.90-2.70(m, 2H), 2.65(t, 2H), 1.77(q, dihydrochloride 2H), 1.39(d, 6H),1.05(t, 3H) 8 4-(5,6-dihydropyridin-1(2H)-yl)- ¹H-NMR(400 MHz, CDCl₃) δ7.60-7.50(m, 2H), N-(4-fluorophenyl)-6- 7.04(t, 2H), 6.00-5.80(m, 2H),5.78(brs, 1H), propylpyrimidin-2-amine 4.29(brs, 1H), 4.00(d, 2H),3.69(s, 1H), 2.65(t, 2H), hydrochloride 2.40-2.20(m, 2H), 1.86(q, 2H),1.03(t, 3H) 9 N-(4-fluorophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 10.53(brs,1H), 7.60- (decahydroquinolin-1(2H)-yl)-6- 7.50(m, 2H), 7.02(t, 2H),5.79(s, 1H), 3.40-3.20(m, propylpyrimidin-2-amine 1H), 2.62(t, 2H),2.10-2.00(m, 1H), 2.00-1.60(m, hydrochloride 11H), 1.50-1.30(m, 4H),1.30-1.10(m, 3H), 1.19(t, 3H) 10 N-(4-fluorophenyl)-4- ¹H-NMR(400 MHz,CDCl₃) δ 7.60-7.50(m, 2H), [decahydroisoquinolin-1(2H)-yl]- 7.03(t, 2H),5.90(d, 1H), 4.40(dd, 1H), 3.75(dd, 1H), 6-propylpyrimidin-2-amine3.40-3.20(m, 2H), 2.70-2.50(m, 2H), 2.10-1.70(m, hydrochloride 5H),1.70-1.50(m, 5H), 1.40-1.20(m, 4H), 1.10- 1.00(m, 3H)

TABLE 1-2 Example Compound NMR Spectrum 11 N-(4-fluorophenyl)-4-(4-¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), phenylpiperidin-1-yl)-6-7.03(t, 2H), 5.90(d, 1H), 4.40(dd, 1H), 3.75(dd, 1H),propylpyrimidin-2-amine 3.40-3.20(m, 2H), 2.70-2.50(m, 2H), 2.10-1.70(m,hydrochloride 5H), 1.70-1.50(m, 5H), 1.40-1.20(m, 4H), 1.10- 1.00(m, 3H)12 N-(4-fluorophenyl)-4-morpholino- ¹H-NMR(400 MHz, CD₃OD) δ7.50-7.40(m, 2H), 6-propylpyrimidin-2-amine 7.15(t, 2H), 6.44(s, 1H),3.80-3.60(m, 8H), 2.62(t, hydrochloride 2H), 1.74(q, 2H), 1.04(t, 3H) 13N-(4-fluorophenyl)-4-(piperazin- ¹H-NMR(400 MHz, CD₃OD) δ 7.60-7.50(m,2H), 1-yl)-6-propylpyrimidin-2-amine 6.98(t, 2H), 6.07(s, 1H), 3.61(t,4H), 2.86(t, 4H), 2.46(t, 2H), 1.71(q, 2H), 0.97(t, 3H) 144-(2-ethylpiperidin-1-yl)-N-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m,2H), fluorophenyl)-6-propylpyrimidin- 6.97(t, 2H), 5.87(s, 1H),4.45-4.30(m, 1H), 4.30- 2-amine 4.10(m, 1H), 2.90(t, 1H), 2.44(t, 2H),1.80-1.40(m, 8H), 0.98(t, 3H), 0.90(t, 3H) 152-{1-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m,2H), propylpyrimidin-4-yl]piperidin-2- 7.00(t, 2H), 6.72(brs, 1H),5.92(s, 1H), 4.95-4.85(m, yl}ethanol 1H), 3.90-3.80(m, 1H), 3.60-3.50(m,1H), 3.30(t, 1H), 2.95(t, 1H), 2.46(t, 2H), 2.10-2.00(m, 1H),1.80-1.60(m, 7H), 1.30-1.20(m, 2H), 0.99(t, 3H) 16 ethyl1-[2-(4-fluorophenylamino)- ¹H-NMR(400 MHz, CDCl₃) δ 7.50-7.40(m, 2H),6-propylpyrimidin-4-yl]piperidin- 6.97(t, 2H), 6.78(brs, 1H), 5.96(s,1H), 4.20-4.10(m, 2-carboxylate 2H), 3.93(brs, 1H), 3.22(t, 1H), 2.48(t,2H), 2.29(d, 1H), 1.90-1.70(m, 6H), 1.70-1.50(m, 1H), 1.45- 1.30(m, 1H),1.23(t, 3H), 0.98(t, 3H) 17 1-[2-(4-fluorophenylamino)-6- ¹H-NMR(400MHz, CDCl₃) δ 7.60-7.50(m, 2H), propylpyrimidin-4-yl]piperidin-4-6.98(t, 2H), 6.88(brs, 1H), 5.92(s, 1H), 5.42(d, 2H), carboxamide4.39(d, 2H), 2.97(t, 2H), 2.50-2.40(m, 3H), 1.97(d, 2H), 1.80-1.60(m,4H), 0.98(t, 3H) 18 {1-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz,CDCl₃) δ 7.60-7.50(m, 2H), propylpyrimidin-4-yl]piperidin-4- 6.97(t,2H), 6.81(brs, 1H), 5.92(s, 1H), 4.40(d, 2H), yl}methanol 3.53(d, 2H),2.88(t, 2H), 2.46(t, 2H), 1.90-1.60(m, 5H), 1.30-1.15(m, 2H), 0.98(t,3H) 19 1-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ7.60-7.50(m, 2H), propylpyrimidin-4-yl]piperidin-4- 7.00(t, 2H),6.84(brs, 1H), 6.00(s, 1H), 3.93(t, 4H), one 2.60-2.40(m, 6H), 1.74(q,2H), 0.99(t, 3H) 20 4-butyl-N-(4-fluorophenyl)-6- ¹H-NMR(400 MHz, CDCl₃)δ 7.60-7.50(m, 2H), (piperidin-1-yl)pyrimidin-2-amine 6.97(t, 2H),6.79(brs, 1H), 5.90(s, 1H), 3.60-3.50(m, 4H), 2.48(t, 2H), 1.70-1.50(m,8H), 1.39(q, 2H), 0.94(t, 3H)

TABLE 1-3 Example Compound NMR Spectrum 214-butyl-6-(2-ethylpiperidin-1-yl)- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m,2H), N-(4-fluorophenyl)pyrimidin-2- 6.97(t, 2H), 6.73(brs, 1H), 5.88(s,1H), 4.50-4.30(m, amine 1H), 4.25-4.15(m, 1H), 2.92(t, 1H), 2.46(t, 2H),1.80-1.55(m, 10H), 1.40(q, 2H), 1.00-0.85(m, 6H) 22 2-{1-[6-butyl-2-(4-¹H-NMR(400 MHz, CDCl₃) δ 7.50-7.40(m, 2H),fluorophenylamino)pyrimidin-4- 6.99(t, 2H), 6.66(brs, 1H), 5.91(s, 1H),4.91(brs, yl]piperidin-2-yl}ethanol 1H), 3.90-3.80(m, 1H), 3.53(d, 1H),3.31(t, 1H), 2.94(t, 1H), 2.48(t, 2H), 2.06(t, 1H), 1.80-1.55(m, 9H),1.42(q, 2H), 0.97(t, 3H) 23 4-butyl-N-(4-fluorophenyl)-6- ¹H-NMR(400MHz, CDCl₃) δ 7.55-7.45(m, 2H), morpholinopyrimidin-2-amine 7.00(t, 2H),6.86(brs, 1H), 5.88(s, 1H), 3.78(t, 4H), 3.58(t, 4H), 2.50(t, 2H),1.70-1.60(m, 2H), 1.39(q, 2H), 0.94(t, 3H) 24 2-{1-[2-(4-chloro-3-¹H-NMR(400 MHz, CDCl₃) δ 8.78(s, 1H), 7.40- nitrophenylamino)-6- 7.30(m,1H), 7.30-7.20(m, 1H), 6.02(s, 1H), 5.00-propylpyrimidin-4-yl]piperidin-2- 4.90(m, 1H), 4.00-3.90(m, 1H),3.60-3.50(m, 1H), yl}ethanol 3.41(t, 1H), 2.98(t, 1H), 2.49(t, 2H),2.20-2.05(m, 1H), 1.80-1.30(m, 9H), 0.97(t, 3H) 25 2-(1-{2-[3-¹H-NMR(400 MHz, CDCl₃) δ 7.67(s, 1H), 7.20- (methylthio)phenylamino]-6-7.10(m, 2H), 7.00-6.80(m, 2H), 5.93(s, 1H),propylpyrimidin-4-yl}piperidin-2- 4.98(brs, 1H), 3.87(brs, 1H),3.60-3.50(m, 1H), yl)ethanol 3.33(t, 1H), 2.95(t, 1H), 2.49(s, 3H),2.50-2.40(m, 1H), 2.10-2.00(m, 1H), 1.80-1.50(m, 9H), 0.99(t, 3H) 264-(2,6-dimethylmorpholino)-N-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m,2H), fluorophenyl)-6-propylpyrimidin- 6.99(t, 2H), 6.84(brs, 1H),5.89(s, 1H), 4.12(d, 2H), 2-amine 3.70-3.55(m, 2H), 2.59(q, 2H), 2.48(t,2H), 1.72(q, 2H), 1.26(d, 6H), 0.98(t, 3H) 278-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H),propylpyrimidin-4-yl]-8- 6.98(t, 2H), 6.80(brs, 1H), 5.81(s, 1H),4.15-4.05(m, azabicyclo[3.2.1]octan-3-ol 1H), 2.45(t, 2H), 2.40-2.25(m,2H), 2.25-2.10(m, 2H), 2.10-2.00(m, 2H), 1.80-1.50(m, 6H), 0.98(t, 3H)28 N-{1-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ7.60-7.45(m, 2H), 7.10- propylpyrimidin-4-yl]piperidin-3- 6.95(m, 2H),6.86(brs, 1H), 5.96(s, 1H), 5.75(brs, yl}acetamide 1H), 4.02(brs, 1H),3.77(d, 1H), 3.65-3.40(m, 3H), 2.46(t, 2H), 1.91(s, 3H), 1.90-1.85(m,1H), 1.80- 1.55(m, 5H), 0.97(t, 3H) 29 N-(4-fluorophenyl)-4-{4-[3-¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H),(piperidin-4-yl)propyl]piperidin-1- 6.98(t, 2H), 6.76(brs, 1H), 5.90(s,1H), 4.33(d, 2H), yl}-6-propylpyrimidin-2-amine 2.84(t, 2H), 2.45(t,2H), 1.80-1.60(m, 5H), 1.60- 1.45(m, 1H), 1.45-1.30(m, 1H), 1.30-1.10(m,4H), 0.98(t, 3H) 30 4-[3-(benzyloxy)piperidin-1-yl]-N- ¹H-NMR(400 MHz,CDCl₃) δ 7.60-7.50(m, 2H), 7.40- (4-fluorophenyl)-6- 7.20(m, 5H),6.97(t, 2H), 6.85(brs, 1H), 5.87(s, 1H), propylpyrimidin-2-amine 4.58(d,2H), 4.20(d, 1H), 3.90-3.80(m, 1H), 3.50- 3.40(m, 1H), 3.30-3.10(m, 2H),2.45(t, 2H), 2.10- 2.00(m, 1H), 2.00-1.80(m, 3H), 1.69(q, 2H), 0.98(t,3H)

TABLE 1-4 Example Compound NMR Spectrum 31 4-(3-oxa-8- ¹H-NMR(400 MHz,CDCl₃) δ 7.55-7.45(m, 2H), azabicyclo[3.2.1]octan-8-yl)-N- 6.97(t, 2H),6.88(brs, 1H), 5.82(s, 1H), 4.41(brs, (4-fluorophenyl)-6- 1H), 3.80(d,2H), 3.61(d, 2H), 3.60-3.40(m, 1H), propylpyrimidin-2-amine 2.47(t, 2H),2.10-1.80(m, 4H), 1.72(q, 2H), 0.98(t, 3H) 32 N-[4-(piperidin-1-yl)-6-¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H), 7.90(s,propylpyrimidin-2-yl]-1H-indol-5- 1H), 7.52(brs, 1H), 7.30-7.20(m, 1H),7.20-7.10(m, amine 1H), 6.50-6.40(m, 1H), 5.85(s, 1H), 3.70-3.50(m, 4H),2.48(t, 2H), 1.74(q, 2H), 1.70-1.50(m, 6H), 0.98(t, 3H) 33N-(3-chloro-4-methylphenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(brs, 1H),7.88(d, (piperidin-1-yl)-6- 1H), 7.21(dd, 1H), 7.12(d, 1H), 5.90(s, 1H),3.70- propylpyrimidin-2-amine 3.60(m, 4H), 2.52(t, 2H), 2.32(s, 3H),1.80-1.60(m, 8H), 0.99(t, 3H) 34 N-[4-(piperidin-1-yl)-6- ¹H-NMR(400MHz, CDCl₃) δ 8.80-8.70(m, 1H), propylpyrimidin-2-yl]quinolin-6- 8.36(d,1H), 8.00(t, 2H), 7.70(d, 1H), 7.40-7.30(m, amine 1H), 7.17(brs, 1H),5.97(s, 1H), 3.97(brs, 1H), 3.70- 3.60(m, 4H), 2.51(t, 2H), 1.80-1.55(m,6H), 1.01(t, 3H) 35 4-(piperidin-1-yl)-6-propyl-N-[3- ¹H-NMR(400 MHz,CDCl₃) δ 8.38(s, 1H), 7.58(brs, (trifluoromethyl)phenyl]pyrimidin- 1H),7.42(d, 1H), 7.35(t, 1H), 5.94(s, 1H), 3.70- 2-amine 3.60(m, 4H),2.49(t, 2H), 1.80-1.55(m, 8H), 0.98(t, 3H) 36 N-[4-(piperidin-1-yl)-6-¹H-NMR(400 MHz, CDCl₃) δ 8.13(s, 1H), 7.60- propylpyrimidin-2-yl]-2-7.50(m, 1H), 7.22(d, 1H), 5.92(s, 1H), 3.60-3.50(m,(trifluoromethyl)-1H- 4H), 2.49(t, 2H), 1.73(q, 2H), 1.70-1.50(m, 6H),benzo[d]imidazol-5-amine 0.93(t, 3H) 37 N-[3-(methylthio)phenyl]-4-¹H-NMR(400 MHz, CDCl₃) δ 9.05(brs, 1H), 7.69(d, (piperidin-1-yl)-6- 1H),7.30-7.15(m, 2H), 6.93(d, 1H), 5.90(s, 1H), propylpyrimidin-2-amine3.70-3.60(m, 4H), 2.55(t, 2H), 2.48(s, 3H), 1.80(q, 2H), 1.70-1.60(m,6H), 1.00(t, 3H) 38 N-(5-methoxy-2-methylphenyl)- ¹H-NMR(400 MHz, CDCl₃)δ 7.76(brs, 1H), 7.05(d, 4-(piperidin-1-yl)-6- 1H), 6.54(d, 1H), 5.90(s,1H), 3.78(s, 3H), 3.70- propylpyrimidin-2-amine 3.55(m, 4H), 2.53(t,2H), 2.30(s, 3H), 1.78(q, 2H), 1.75-1.55(m, 6H), 1.90(t, 3H) 39N-(5-chloro-2-methylphenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(brs, 1H),7.05(d, (piperidin-1-yl)-6- 1H), 6.87(d, 1H), 5.92(s, 1H), 3.65-3.55(m,4H), propylpyrimidin-2-amine 2.49(t, 2H), 2.29(s, 3H), 1.80-1.60(m, 8H),0.99(t, 3H) 40 N-(4-fluoro-3-nitrophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ9.00-8.90(m, 1H), (piperidin-1-yl)-6- 7.82(brs, 1H), 7.50-7.40(m, 1H),7.17(t, 1H), 5.97(s, propylpyrimidin-2-amine 1H), 3.70-3.60(m, 4H),2.50(t, 2H), 1.80-1.60(m, 8H), 0.99(t, 3H)

TABLE 1-5 Example Compound NMR Spectrum 41 N-(4-methoxyphenyl)-4-¹H-NMR(400 MHz, CDCl₃) δ 8.11(brs, 1H), 7.48(dd, (piperidin-1-yl)-6-2H), 6.85(dd, 2H), 5.86(s, 1H), 3.79(s, 3H), 3.65-propylpyrimidin-2-amine 3.55(m, 4H), 2.51(t, 2H), 1.77(q, 2H),1.70-1.55(m, 6H), 0.99(t, 3H) 42 N-(3-methoxyphenyl)-4- ¹H-NMR(400 MHz,CDCl₃) δ 7.98(brs, 1H), 7.46(s, (piperidin-1-yl)-6- 1H), 7.17(t, 1H),7.02(d, 1H), 6.56(d, 1H), 5.90(s, propylpyrimidin-2-amine 1H), 3.80(s,3H), 3.70-3.60(m, 4H), 2.51(t, 2H), 1.80-1.55(m, 8H), 0.99(t, 3H) 43N-(3-chlorophenyl)-4-(piperidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.50(brs, 1H),7.92(s, 1-yl)-6-propylpyrimidin-2-amine 1H), 7.23(d, 1H), 7.20(t, 1H),6.98(d, 1H), 5.93(s, 1H), 3.70-3.60(m, 4H), 2.53(t, 2H), 1.80-1.60(m,8H), 1.00(t, 3H) 44 N-(3-nitrophenyl)-4-(piperidin-1- ¹H-NMR(400 MHz,CDCl₃) δ 9.10(d, 1H), 7.86(brs, yl)-6-propylpyrimidin-2-amine 1H),7.79(d, 1H), 7.51(d, 1H), 7.38(t, 1H), 5.98(s, 1H), 3.70-3.60(m, 4H),2.51(t, 2H), 1.80-1.60(m, 8H), 0.99(t, 3H) 45N-(4-chloro-3-nitrophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.83(s, 1H),7.84(brs, (piperidin-1-yl)-6- 1H), 7.40-7.30(m, 2H), 5.98(s, 1H),3.70-3.60(m, propylpyrimidin-2-amine 4H), 2.50(t, 2H), 1.80-1.60(m, 8H),0.99(t, 3H) 46 3-[4-(piperidin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ8.39(brs, 1H), 8.24(s, propylpyrimidin-2- 1H), 7.61(d, 1H), 7.36(t, 1H),7.26(d, 1H), 5.97(s, ylamino]benzonitrile 1H), 3.70-3.60(m, 4H), 2.53(t,2H), 1.80-1.60(m, 8H), 1.00(t, 3H) 47 N-(4-methyl-3-nitrophenyl)-4-¹H-NMR(400 MHz, CDCl₃) δ 8.85(d, 1H), 7.32(d, (piperidin-1-yl)-6- 1H),7.18(d, 1H), 5.95(s, 1H), 3.70-3.60(m, 4H), propylpyrimidin-2-amine2.53(s, 3H), 2.47(t, 2H), 1.80-1.60(m, 8H), 0.98(t, 3H) 484-(4-ethylpiperazin-1-yl)-N-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.53-7.48(m,2H), fluorophenyl)-6-methylpyrimidin- 7.20(s, 1H), 7.00-6.94(m, 2H),5.90(s, 1H), 3.63(dd, 2-amine 4H), 2.51-2.42(m, 6H), 2.25(s, 3H),1.12(dd, 3H) 49 N-(4-fluorophenyl)-4-[4-(4- ¹H-NMR(400 MHz, CDCl₃) δ7.54-7.50(m, 2H), 7.03- methoxyphenyl)piperazin-1-yl]-6- 6.87(m, 7H),5.96(s, 1H), 3.77(s, 3H), 3.76(dd, 4H), methylpyrimidin-2-amine 3.12(dd,4H), 2.78(s, 3H) 50 N-(4-fluorophenyl)-4-[4-(4- ¹H-NMR(400 MHz, CDCl₃) δ7.54-7.49(m, 2H), 7.03- fluorophenyl)piperazin-1-yl]-6- 6.87(m, 7H),5.96(s, 1H), 3.76(dd, 4H), 3.16(dd, methylpyrimidin-2-amine 4H), 2.28(s,3H)

TABLE 1-6 Example Compound NMR Spectrum 51N-(4-fluorophenyl)-4-methyl-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.52-7.47(m,2H), 7.01- (morpholin-4-yl)pyrimidin-2- 6.95(m, 2H), 6.89(s, 1H),5.89(s, 1H), 3.77(dd, 4H), amine 3.57(dd, 4H), 2.27(s, 3H) 521-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.53-7.50(m, 2H),7.02- methylpyrimidin-4-yl]piperidin-4- 6.98(m, 2H), 6.90(s, 1H),6.02(s, 1H), 3.93(dd, 4H), one 2.53(dd, 4H), 2.30(s, 3H) 53N-(4-fluorophenyl)-4-methyl-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.53-7.50(m,2H), 6.99- (piperidin-1-yl)pyrimidin-2-amine 6.95(m, 3H), 5.91(s, 1H),3.57(dd, 4H), 2.24(s, 3H), 1.69-1.57(m, 6H) 54 4-(azetidin-1-yl)-N-(4-¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.57(m, 2H), 6.98-fluorophenyl)-6-methylpyrimidin- 6.91(m, 3H), 5.56(s, 1H), 4.07(dd, 4H),2.43- 2-amine 2.36(m, 2H), 2.24(s, 3H) 55 1-[2-(4-fluorophenylamino)-6-¹H-NMR(400 MHz, CDCl₃) δ 7.53-7.50(m, 2H), 7.02-methylpyrimidin-4-yl]piperidin-3- 6.97(m, 2H), 5.96(s, 1H), 4.12-4.08(m,3H), 3.76(d, ol 1H), 3.72-3.66(m, 1H), 3.36-3.05(m, 2H), 2.23(s, 3H),2.22-2.20(m, 1H), 1.85-1.81(m, 1H), 1.58- 1.51(m, 2H) 561-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.52-7.49(m, 2H),7.00- methylpyrimidin-4-yl]piperidin-4- 6.95(m, 2H), 5.93(s, 1H),4.07-4.03(m, 2H), 3.96- ol 3.92(m, 1H), 3.22(m, 2H), 2.25(s, 3H),1.97-1.90(m, 2H), 1.58-1.50(m, 2H) 57 N-(4-fluorophenyl)-4-methyl-6-¹H-NMR(400 MHz, CDCl₃) δ 7.55-7.50(m, 2H), 7.01-(2-methylpiperidin-1-yl)pyrimidin- 6.95(m, 2H), 6.79(brs, 1H), 5.89(s,1H), 4.61(brs, 2-amine 1H), 4.21(d, 1H), 3.93(m, 1H), 2.25(s, 3H), 1.77-1.61(m, 6H), 1.18(d, 3H) 58 N-(4-fluorophenyl)-4-methyl-6- ¹H-NMR(400MHz, CDCl₃) δ 7.54-7.51(m, 2H), 7.00- (3-methylpiperidin-1-yl)pyrimidin-6.96(m, 2H), 6.76(brs, 1H), 5.91(s, 1H), 4.21(brs, 2-amine 2H), 2.86(m,1H), 2.53(dd, 1H), 2.25(s, 3H), 1.86(dd, 1H), 1.75-1.61(m, 2H),1.54-1.49(m, 1H), 1.22-1.16(m, 1H), 0.95(d, 3H) 594-(3,5-cis-dimethylpiperidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 7.55-7.50(m,2H), 6.99- yl)-N-(4-fluorophenyl)-6- 6.94(m, 3H), 5.91(s, 1H), 4.28(d,2H), 2.53(dd, 1H), methylpyrimidin-2-amine 2.32(dd, 2H), 2.25(s, 3H),1.84(d, 1H), 1.67-1.57(m, 2H), 0.94(d, 6H). 0.77(m, 1H) 604-(azepan-1-yl)-N-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.57-7.54(m, 2H), 6.99-fluorophenyl)-6-methylpyrimidin- 6.94(m, 2H), 6.85(brs, 1H), 5.81(s,1H), 3.59- 2-amine 3.35(m, 4H), 2.25(s, 3H), 1.79(brs, 4H), 1.56(dd, 4H)

TABLE 1-7 Example Compound NMR Spectrum 614-(2-ethylpiperidin-1-yl)-N-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.54-7.49(m,2H), fluorophenyl)-6-methylpyrimidin- 7.07(brs, 1H), 6.99-6.93(m, 2H),5.88(s, 1H), 2-amine 4.38(brs, 1H), 4.21(brs, 1H), 2.91(m, 1H), 2.23(s,3H), 1.74-1.58(m, 7H), 1.50-1.45(m, 1H), 0.89(dd, 3H) 624-((2R,6S)-2,6-dimethylpiperidin- ¹H-NMR(400 MHz, CDCl₃) δ 7.56-7.50(m,2H), 7.00- 1-yl)-N-(4-fluorophenyl)-6- 6.94(m, 2H), 6.78(brs, 1H),5.87(s, 1H), 4.55(brs, methylpyrimidin-2-amine 2H), 2.25(s, 3H),1.89-1.82(m, 1H), 1.75-1.69(m, 4H), 1.68-1.52(m, 1H), 1.25(s, 3H),1.23(s, 3H) 63 N-(4-fluorophenyl)-4-methyl-6- ¹H-NMR(400 MHz, CDCl₃) δ7.55-7.51(m, 2H), 7.33- (4-phenylpiperidin-1-yl)pyrimidin- 7.30(m, 2H),7.24-7.22(m, 2H), 7.00-6.96(m, 2H), 2-amine 6.82(brs, 1H), 5.98(s, 1H),4.51(d, 2H), 2.97(m, 2H), 2.85-2.74(m, 1H), 2.28(s, 3H), 1.94(d, 2H),1.76- 1.69(m, 2H) 64 N-(4-fluorophenyl)-4-methyl-6- ¹H-NMR(400 MHz,CDCl₃) δ 7.53-7.48(m, 2H), 7.02- (piperazin-1-yl)pyrimidin-2- 6.95(m,3H), 5.90(s, 1H), 3.59(dd, 4H), 2.93(dd, amine 4H), 2.27(s, 3H) 65N-(4-fluorophenyl)-4-methyl-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.51-7.49(m,2H), (4-methylpiperazin-1- 7.05(brs, 1H), 7.01-6.96(m, 2H), 5.91(s, 1H),yl)pyrimidin-2-amine 3.62(dd, 4H), 2.46(dd, 4H), 2.33(s, 3H), 2.26(s,3H) 66 4-(2,5-dimethylpiperazin-1-yl)-N- ¹H-NMR(400 MHz, CDCl₃) δ7.53-7.50(m, 2H), 7.00- (4-fluorophenyl)-6- 6.96(m, 2H), 6.91(brs, 1H),5.86(s, 1H), 4.33(dd, methylpyrimidin-2-amine 1H), 3.88(dd, 1H),3.33-3.29(m, 3H), 2.65(dd, 1H), 2.27(s, 3H), 1.27(d, 3H), 1.20(d, 3H) 674-(3,5-dimethylpiperazin-1-yl)-N- ¹H-NMR(400 MHz, CDCl₃) δ 7.54-7.50(m,2H), 7.00- (4-fluorophenyl)-6- 6.96(m, 2H), 6.89(brs, 1H), 5.91(s, 1H),4.21(d, 2H), methylpyrimidin-2-amine 2.89-2.84(m, 2H), 2.45(dd, 2H),2.26(s, 3H), 1.14(s, 3H), 1.13(s, 3H) 68 N-(4-fluorophenyl)-4-methyl-6-¹H-NMR(400 MHz, CDCl₃) δ 7.56-7.52(m, 2H), (octahydroquinolin-1(2H)-7.07(brs, 1H), 6.99-6.94(m, 2H), 5.78(s, 1H), yl)pyrimidin-2-amine4.17(dd, 1H), 3.29(m, 1H), 3.16(m, 1H), 2.24(s, 3H), 2.16(dd, 1H),1.86-1.61(m, 6H), 1.49-1.09(m, 6H) 69 N-(4-fluorophenyl)-4-methyl-6-¹H-NMR(400 MHz, CDCl₃) δ 7.54-7.50(m, 2H), (octahydroisoquinolin-2(1H)-7.11(brs, 1H), 7.00-6.95(m, 2H), 5.89(s, 1H), yl)pyrimidin-2-amine4.05(brs, 1H), 3.89(brs, 1H), 3.22(d, 1H), 3.13(dd, 1H), 2.24(s, 3H),1.92-1.88(m, 1H), 1.82-1.78(m, 2H), 1.76-1.24(m, 9H) 704-(5,6-dihydropyridin-1(2H)-yl)- ¹H-NMR(400 MHz, CDCl₃) δ 7.56-7.50(m,2H), N-(4-fluorophenyl)-6- 7.08(brs, 1H), 7.08-6.96(m, 2H), 5.94-5.89(m,2H), methylpyrimidin-2-amine 5.78-5.75(m, 1H), 4.00(brs, 2H), 3.74(dd,2H), 2.26- 2.22(m, 5H)

TABLE 1-8 Example Compound NMR Spectrum 712-{1-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.47-7.43(m,2H), 7.02- methylpyrimidin-4-yl]piperidin-2- 6.97(m, 2H), 6.87(brs, 1H),5.93(s, 1H), 4.90(brs, yl}ethanol 1H), 3.82(brs, 1H), 3.55-3.50(m, 1H),3.28(dd, 1H), 2.93(m, 1H), 2.25(s, 3H), 2.08(dd, 1H), 1.78- 1.28(m, 7H)72 2-{1-[2-(4-fluorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ7.49-7.45(m, 2H), 7.01- methylpyrimidin-4-yl]piperidin-2- 6.94(m, 3H),5.93(s, 1H), 4.68(brs, 1H), 4.11(brs, yl}methanol 1H), 3.90(dd, 1H),3.70(dd, 1H), 3.00(dd, 1H), 2.21(s, 3H), 1.81-1.49(m, 6H) 73N-[4-(octahydroquinolin-1(2H)- ¹H-NMR(400 MHz, CDCl₃) δ 8.09(brs, 1H),7.97(s, yl)-6-propylpyrimidin-2-yl]-1H- 1H), 7.49(d, 1H), 7.12-7.08(m,2H), 6.89(brs, 1H), indol-6-amine 6.46(s, 1H), 5.75(s, 1H), 4.26(dd,2H), 3.32(m, 1H), 3.18-3.15(m, 1H), 2.46(dd, 2H), 2.23(dd, 1H), 1.89-1.50(m, 10H), 1.38-1.26(m, 2H), 1.16-1.10(m, 2H), 0.99(t, 3H) 742-{1-[2-(1H-indol-6-ylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.44(brs, 1H),7.95(s, propylpyrimidin-4-yl]piperidin-2- 1H), 7.49(d, 1H), 7.07(dd,1H), 6.99(dd, 2H), 6.43(s, yl}ethanol 1H), 5.88(s, 1H), 5.05(brs, 1H),3.84-3.72(m, 1H), 3.55-3.53(m, 1H), 3.45-3.38(m, 1H), 2.99-2.93(m, 1H),2.47(dd, 2H), 2.11-2.05(m, 1H), 1.78-1.44(m, 9H), 0.99(t, 3H) 752-{1-[2-(1H-indol-6-ylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 12.00(brs, 1H),propylpyrimidin-4-yl]piperidin-2- 10.26(brs, 1H), 9.95(s, 1H), 8.64(s,1H), 7.26(d, yl}ethanol hydrochloride 1H), 7.14(t, 1H), 6.71(d, 1H),6.35(s, 1H), 5.60- 5.40(m, 2H), 5.29(s, 1H), 4.10-4.00(m, 1H), 3.79(brs,1H), 3.65-3.50(m, 1H), 3.20(t, 1H), 2.15- 2.05(m, 2H), 2.05-2.00(m, 1H),1.90-1.60(m, 6H), 1.50-1.35(m, 3H), 0.85(t, 3H) 76N-[4-(piperidin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.12(brs, 1H), 7.98(s,propylpyrimidin-2-yl]-1H-indol-6- 1H), 7.49(d, 1H), 7.10-7.06(m, 2H),6.96(brs, 1H), amine 6.47(dd, 1H), 5.89(s, 1H), 3.61(dd, 4H), 2.47(dd,2H), 1.77-1.61(m, 8H), 0.97(t, 3H) 77 N-(4-morpholino-6- ¹H-NMR(400 MHz,CDCl₃) δ 8.18(brs, 1H), 7.90(s, propylpyrimidin-2-yl)-1H-indol-6- 1H),7.51(d, 1H), 7.11-7.07(m, 2H), 6.95(brs, 1H), amine 6.48(dd, 1H),5.89(s, 1H), 3.77(dd, 4H), 3.60(dd, 4H), 2.50(dd, 2H), 1.77-1.72(m, 2H),0.99(t, 3H) 78 N-[4-(2-ethylpiperidin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ8.08(brs, 1H), 7.98(s, propylpyrimidin-2-yl]-1H-indol-6- 1H), 7.49(d,1H), 7.10-7.07(m, 2H), 6.89(brs, 1H), amine 6.47(dd, 1H), 5.86(s, 1H),4.44(brs, 1H), 4.28(brs, 1H), 2.92(m, 1H), 2.46(dd, 2H), 1.78-1.61(m,9H), 1.54-1.48(m, 1H), 1.05(dd, 3H), 0.97(t, 3H) 79 N-(4-morpholino-6-¹H-NMR(400 MHz, CD₃OD) δ 7.58-7.56(m, 2H),propylpyrimidin-2-yl)-1H-indol-6- 7.27(d, 1H), 7.00(dd, 1H), 6.46(d,1H), 6.39(s, 1H), amine hydrochloride 3.81-3.75(m, 8H), 2.60(dd, 2H),1.77-1.71(m, 2H), 1.03(dd, 3H)

TABLE 1-9 Example Compound NMR Spectrum 80(R)-3-[4-(3-ethylmorpholino)-6- ¹H-NMR(400 MHz, CD₃OD) δ 8.16(s, 1H),7.59(dd, propylpyrimidin-2- 1H), 7.34(dd, 1H), 7.23(d, 1H), 5.89(s, 1H),ylamino]benzonitrile 4.08(brs, 1H), 4.00-3.94(m, 3H), 3.64-3.53(m, 2H),3.28(m, 1H), 2.49(dd, 2H), 1.96-1.68(m, 4H), 0.99- 0.91(m, 6H) 81(R)-tert-butyl 4-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.22(s, 1H), 7.58(d,cyanophenylamino)-6- 1H), 7.35(dd, 1H), 7.23(d, 1H), 7.02(brs, 1H),propylpyrimidin-4-yl]-3- 5.93(s, 1H), 4.54-3.95(m, 4H), 3.27-2.99(m,3H), methylpiperazin-1-carboxylate 2.50(dd, 2H), 1.76-1.70(m, 2H),1.49(s, 3H), 1.24(d, 3H), 0.99(t, 3H) 82 (R)-3-[4-(2-methylpiperazin-1-¹H-NMR(400 MHz, CD₃OD) δ 8.00(s, 1H), 7.78(d, yl)-6-propylpyrimidin-2-1H), 7.62-7.58(m, 2H), 6.64(s, 1H), 3.54-3.24(m, ylamino]benzonitrile7H), 2.71(dd, 2H), 1.83-1.78(m, 2H), 1.47(d, 3H), dihydrochloride1.06(t, 3H) 83 4-morpholino-N-(3-nitrophenyl)- ¹H-NMR(400 MHz, CDCl₃) δ11.30(s, 1H), 9.05(dd, 6-propylpyrimidin-2-amine 1H), 7.98(dd, 1H),7.64(dd, 1H), 7.51(dd, 1H), hydrochloride 6.01(s, 1H), 3.88(brs, 8H),2.68(dd, 2H), 1.92- 1.84(m, 2H), 1.04(t, 3H) 84N-(4-fluoro-3-nitrophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 11.24(s, 1H),8.88(d, morpholino-6-propylpyrimidin-2- 1H), 7.61(d, 1H), 7.28(d, 1H),6.03(s, 1H), 3.87(brs, amine hydrochloride 8H), 2.68(dd, 2H),1.91-1.85(m, 2H), 1.04(t, 3H) 85 N-(4-chloro-3-nitrophenyl)-4-¹H-NMR(400 MHz, CDCl₃) δ 11.39(s, 1H), 8.74(s,morpholino-6-propylpyrimidin-2- 1H), 7.57(s, 2H), 6.02(s, 1H), 3.87(brs,8H), amine hydrochloride 2.68(dd, 2H), 1.91-1.83(m, 2H), 1.04(t, 3H) 86N-(3-methoxyphenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 13.86(brs, 1H), 10.56(s,morpholino-6-propylpyrimidin-2- 1H), 7.28-7.12(m, 3H), 6.69(dd, 1H),5.96(s, 1H), amine hydrochloride 3.79(s, 3H), 3.96-3.61(m, 8H), 2.64(dd,2H), 1.89- 1.83(m, 2H), 1.02(t, 3H) 87 N-(4-methoxyphenyl)-4- ¹H-NMR(400MHz, CDCl₃) δ 10.29(s, 1H), 7.42(d, morpholino-6-propylpyrimidin-2- 2H),6.87(d, 2H), 5.87(s, 1H), 3.80(s, 3H), 3.80- amine hydrochloride 3.71(m,8H), 2.64(dd, 2H), 1.89-1.83(m, 2H), 1.02(t, 3H) 88N-[3-(methylthio)phenyl]-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.51(s, 1H), 7.31-morpholino-6-propylpyrimidin-2- 7.23(m, 2H), 7.01(d, 1H), 5.98(dd, 1H),3.93- amine hydrochloride 3.64(m, 8H), 2.64(dd, 2H), 2.46(s, 3H), 1.89-1.83(m, 2H), 1.03(t, 3H) 89 N-(3-chlorophenyl)-4- ¹H-NMR(400 MHz, CDCl₃)δ 13.97(brs, 1H), 10.79(s, morpholino-6-propylpyrimidin-2- 1H), 7.78(s,1H), 7.36(d, 1H), 7.26(dd, 1H), 7.11(d, amine hydrochloride 1H), 5.94(s,1H), 3.83(brs, 8H), 2.66(dd, 2H), 1.90- 1.84(m, 2H), 1.03(t, 3H)

TABLE 1-10 Example Compound NMR Spectrum 90N-(3-chloro-4-methylphenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 13.83(brs, 1H),10.64(s, morpholino-6-propylpyrimidin-2- 1H), 7.74(d, 1H), 7.25(dd, 1H),7.17(d, 1H), 5.95(s, amine hydrochloride 1H), 3.90-3.65(m, 8H), 2.64(dd,2H), 2.33(s, 3H), 1.89-1.84(m, 2H), 1.02(t, 3H) 914-morpholino-6-propyl-N-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.28(s, 1H),8.26(brs, (trifluoromethyl)phenyl]pyrimidin- 1H), 7.47(d, 1H), 7.39(dd,1H), 7.26(d, 1H), 5.94(s, 2-amine hydrochloride 1H), 3.80(brs, 4H),3.67(brs, 4H), 2.55(dd, 2H), 1.81-1.75(m, 2H), 1.00(t, 3H) 92N-(4-morpholino-6- ¹H-NMR(400 MHz, CD₃OD) δ 7.61(s, 1H), 7.45(d,propylpyrimidin-2-yl)-1H-indol-5- 1H), 7.32(s, 1H), 7.14(d, 1H), 6.48(s,1H), 6.38(s, amine hydrochloride 1H), 3.80-3.74(m, 8H), 2.60(dd, 2H),1.85-1.71(m, 2H), 1.04(t, 3H) 93 N-(4-morpholino-6- ¹H-NMR(400 MHz,CD₃OD) δ 8.03(s, 1H), 7.74(d, propylpyrimidin-2-yl)-2- 1H), 7.45(d, 1H),6.48(s, 1H), 3.85-3.78(m, 8H), (trifluoromethyl)-1H- 2.66(dd, 2H),1.82-1.76(m, 2H), 1.07(t, 3H) benzo[d]imidazol-6-amine hydrochloride 94N-(4-morpholino-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.55(d, 1H), 8.08(d,propylpyrimidin-2-yl)quinolin-6- 1H), 7.97(d, 1H), 7.87(s, 1H), 7.41(dd,1H), 5.99(s, amine hydrochloride 1H), 3.83(brs, 8H), 2.66(dd, 2H),1.91-1.85(m, 2H), 1.03(t, 3H) 95 3-(4-morpholino-6- ¹H-NMR(400 MHz,CDCl₃) δ 8.07(s, 1H), 7.70(d, propylpyrimidin-2- 1H), 7.48-7.41(m, 2H),6.04(s, 1H), 3.85(brs, 8H), ylamino)benzonitrile 2.67(dd, 2H),1.91-1.85(m, 2H), 1.03(t, 3H) 96 N-(5-methoxy-2-methylphenyl)-¹H-NMR(400 MHz, CDCl₃) δ 7.94(s, 1H), 7.04(d,4-morpholino-6-propylpyrimidin- 1H), 6.62(brs, 1H), 6.50(d, 1H), 5.89(d,1H), 3.79(s, 2-amine 3H), 3.79-3.77(m, 4H), 3.61(s, 4H), 2.50(dd, 2H),2.25(s, 3H), 1.77-1.71(m, 2H), 0.98(t, 3H) 97N-(5-chloro-2-methylphenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(s, 1H),7.04(d, morpholino-6-propylpyrimidin-2- 1H), 6.88(d, 1H), 6.62(brs, 1H),5.91(d, 1H), 3.80- amine 3.74(m, 4H), 3.62-3.57(m, 4H), 2.49(dd, 2H),2.27(s, 3H), 1.77-1.71(m, 2H), 0.98(t, 3H) 98 N-(4-morpholino-6-¹H-NMR(400 MHz, CDCl₃) δ 9.01(s, 1H), 8.54(s,propylpyrimidin-2-yl)quinolin-3- 1H), 8.02(d, 1H), 7.71(d, 1H),7.55-7.49(m, 2H), amine 7.32(brs, 1H), 5.96(d, 1H), 3.79(s, 4H), 3.63(s,4H), 2.54(dd, 2H), 1.80-1.72(m, 2H), 1.00(t, 3H) 994-(2-ethylpiperidin-1-yl)-N-(3- ¹H-NMR(400 MHz, CDCl₃) δ 9.10(s, 1H),7.77(d, nitrophenyl)-6-propylpyrimidin-2- 1H), 7.50(d, 1H), 7.37(dd,1H), 7.19(brs, 1H), amine 5.95(s, 1H), 4.47(brs, 1H), 4.33(brs, 1H),3.00(dd, 1H), 2.48(dd, 2H), 1.82-1.53(m, 10H), 1.00(t, 3H), 0.89(t, 3H)

TABLE 1-11 Example Compound NMR Spectrum 1004-(2-ethylpiperidin-1-yl)-N-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.93(d, 1H),7.43(brs, fluoro-3-nitrophenyl)-6- 2H), 7.16(dd, 1H), 5.95(s, 1H),4.44(brs, 1H), propylpyrimidin-2-amine 4.29(brs, 1H), 3.00(dd, 1H),2.48(dd, 2H), 1.78- 1.49(m, 10H), 0.98(t, 3H), 0.89(t, 3H) 101N-(4-chloro-3-nitrophenyl)-4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.81(s, 1H),7.36- ethylpiperidin-1-yl)-6- 7.26(m, 3H), 5.95(s, 1H), 4.41(brs, 1H),4.27(brs, propylpyrimidin-2-amine 1H), 2.97(dd, 1H), 2.47(dd, 2H),1.78-1.48(m, 10H), 0.98(t, 3H), 0.88(t, 3H) 1024-(2-ethylpiperidin-1-yl)-N-(3- ¹H-NMR(400 MHz, CDCl₃) δ 7.49(s, 1H),7.16(dd, methoxyphenyl)-6- 2H), 7.01(d, 1H), 6.52(d, 1H), 5.87(s, 1H),4.42(brs, propylpyrimidin-2-amine 1H), 4.31(brs, 1H), 3.80(s, 3H),2.94(dd, 1H), 2.46(dd, 2H), 1.78-1.47(m, 10H), 0.98(t, 3H), 0.90(t, 3H)103 4-(2-ethylpiperidin-1-yl)-N-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.08(brs,1H), 7.49(d, methoxyphenyl)-6- 2H), 6.85(d, 2H), 5.84(s, 1H), 4.42(brs,1H), propylpyrimidin-2-amine 4.24(brs, 1H), 3.79(s, 3H), 2.95(dd, 1H),2.50(dd, 2H), 1.79-1.47(m, 10H), 0.99(t, 3H), 0.89(t, 3H) 1044-(2-ethylpiperidin-1-yl)-N-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.88(brs, 1H),7.73(s, (methylthio)phenyl]-6- 1H), 7.25(d, 1H), 7.18(dd, 1H), 6.88(d,1H), 5.88(s, propylpyrimidin-2-amine 1H), 4.44(brs, 1H), 4.30(brs, 1H),2.97(dd, 1H), 2.51-2.48(m, 2H), 2.48(s, 3H), 1.76-1.51(m, 10H), 0.99(t,3H), 0.90(t, 3H) 105 N-(3-chlorophenyl)-4-(2- ¹H-NMR(400 MHz, CDCl₃) δ7.95(s, 1H), 7.49(brs, ethylpiperidin-1-yl)-6- 1H), 7.26(d, 1H),7.17(dd, 1H), 6.93(d, 1H), 5.90(s, propylpyrimidin-2-amine 1H),4.45(brs, 1H), 4.24(brs, 1H), 2.98(dd, 1H), 2.48(dd, 2H), 1.76-1.49(m,10H), 0.99(t, 3H), 0.92(t, 3H) 106 N-(3-chloro-4-methylphenyl)-4-¹H-NMR(400 MHz, CDCl₃) δ 7.92(s, 1H), 7.17(d, (2-ethylpiperidin-1-yl)-6-1H), 7.08(d, 1H), 6.85(brs, 1H), 5.87(s, 1H), propylpyrimidin-2-amine4.43(brs, 1H), 4.23(brs, 1H), 2.95(dd, 1H), 2.44(dd, 2H), 2.31(s, 3H),1.74-1.48(m, 10H), 0.98(t, 3H), 0.91(t, 3H) 1074-(2-ethylpiperidin-1-yl)-6-propyl- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(s,1H), 7.96(brs, N-[3- 1H), 7.45(d, 1H), 7.36(dd, 1H), 7.22(d, 1H),5.92(s, (trifluoromethyl)phenyl]pyrimidin- 1H), 4.45(brs, 1H), 4.29(brs,1H), 2.99(dd, 1H), 2-amine 2.50(dd, 2H), 1.81-1.49(m, 10H), 0.99(t, 3H),0.88(t, 3H) 108 N-[4-(2-ethylpiperidin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ9.42(brs, 1H), 8.50(brs, propylpyrimidin-2-yl]-1H-indol-5- 1H), 7.86(s,1H), 7.33-7.25(m, 2H), 7.21(s, 1H), amine 6.46(s, 1H), 5.84(s, 1H),4.49-4.11(m, 2H), 3.00(dd, 1H), 2.55(dd, 2H), 1.86-1.50(m, 10H), 1.00(t,3H), 0.90(t, 3H) 109 N-[4-(2-ethylpiperidin-1-yl)-6- ¹H-NMR(400 MHz,CDCl₃) δ 9.66(brs, 1H), 8.35(brs, propylpyrimidin-2-yl]-2- 1H), 8.11(s,1H), 7.59(d, 1H), 7.28(d, 1H), 5.90(s, (trifluoromethyl)-1H- 1H),4.35(brs, 2H), 2.89(dd, 1H), 2.49(dd, 2H), 1.77-benzo[d]imidazol-6-amine 1.44(m, 10H), 0.94(t, 3H), 0.84(t, 3H)

TABLE 1-12 Example Compound NMR Spectrum 110N-[4-(2-ethylpiperidin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.74(d, 1H),8.34(d, propylpyrimidin-2-yl]quinolin-6- 1H), 8.00(dd, 2H), 7.72(dd,1H), 7.32(dd, 1H), amine 7.16(brs, 1H), 5.94(s, 1H), 4.48(brs, 1H),4.31(brs, 1H), 2.99(dd, 1H), 2.50(dd, 2H), 1.82-1.51(m, 10H), 1.00(t,3H), 0.90(t, 3H) 111 3-[4-(2-ethylpiperidin-1-yl)-6- ¹H-NMR(400 MHz,CDCl₃) δ 8.26(s, 1H), 7.56(d, propylpyrimidin-2- 1H), 7.33(dd, 1H),7.20(d, 1H), 7.04(brs, 1H), ylamino]benzonitrile 5.94(s, 1H), 4.41(brs,1H), 4.22(brs, 1H), 2.97(m, 1H), 2.47(dd, 2H), 1.79-1.48(m, 10H),0.98(t, 3H), 0.89(t, 3H) 112 4-(2-ethylpiperidin-1-yl)-N-(5- ¹H-NMR(400MHz, CDCl₃) δ 8.02(s, 1H), 7.02(d, methoxy-2-methylphenyl)-6- 1H),6.62(brs, 1H), 6.47(dd, 1H), 5.88(s, 1H), propylpyrimidin-2-amine4.38(brs, 2H), 3.79(s, 3H), 2.90(dd, 1H), 2.48(dd, 2H), 2.25(s, 3H),1.77-1.45(m, 10H), 0.98(t, 3H), 0.89(t, 3H) 113N-(5-chloro-2-methylphenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.46(s, 1H),7.04(d, (2-ethylpiperidin-1-yl)-6- 1H), 6.85(d, 1H), 6.57(brs, 1H),5.90(s, 1H), propylpyrimidin-2-amine 4.42(brs, 1H), 4.25(brs, 1H),2.95(dd, 1H), 2.46(dd, 2H), 2.27(s, 3H), 1.75-1.48(m, 10H), 0.97(t, 3H),0.89(t, 3H) 114 N-[4-(2-ethylpiperidin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ8.93(d, 1H), 8.67(d, propylpyrimidin-2-yl]quinolin-3- 1H), 8.01(d, 1H),7.71(d, 1H), 7.55-7.46(m, 2H), amine 7.26(brs, 1H), 5.96(s, 1H),4.46(brs, 1H), 4.31(brs, 1H), 2.98(m, 1H), 2.51(dd, 2H), 1.81-1.50(m,10H), 1.00(t, 3H), 0.91(t, 3H) 115 N-(4-chloro-3-nitrophenyl)-4-(2-¹H-NMR(400 MHz, CDCl₃) δ 8.80(d, 1H), 8.23(s, ethylpiperidin-1-yl)-6-1H), 7.53-7.47(m, 2H), 5.99(s, 1H), 5.11-3.21(m, propylpyrimidin-2-amine5H), 2.63(dd, 2H), 1.91-1.54(m, 10H), 1.03(t, 3H), hydrochloride 0.94(t,3H) 116 3-[4-(2-ethylpiperidin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ13.60(brs, 1H), propylpyrimidin-2- 11.04(brs, 1H), 8.23(s, 1H), 7.66(d,1H), 7.45- ylamino]benzonitrile 7.26(m, 2H), 5.96(brs, 1H), 4.89(brd,1H), 3.90(brd, hydrochloride 1H), 3.15(brd, 1H), 2.65-2.62(m, 2H),1.90-1.54(m, 10H), 1.04(t, 3H), 0.94(brs, 3H) 117(R)-N-(4-chloro-3-nitrophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.85(d, 1H),7.55(brs, (2-methylpiperazin-1-yl)-6- 1H), 7.40(d, 1H), 7.32(dd, 1H),5.95(s, 1H), propylpyrimidin-2-amine 4.54(brs, 1H), 4.10(d, 1H),3.25-3.19(m, 2H), 3.07- 3.04(m, 2H), 2.85(dd, 1H), 2.51(dd, 2H), 1.77-1.69(m, 2H), 1.35(d, 3H), 0.98(t, 3H) 118 (R)-N-[4-(2-methylpiperazin-1-¹H-NMR(400 MHz, CD₃OD) δ 7.68(s, 1H), 7.50(d,yl)-6-propylpyrimidin-2-yl]-1H- 1H), 7.20(d, 1H), 7.03(d, 1H), 6.41(d,1H), 6.28(s, indol-6-amine 1H), 4.87(brs, 1H), 4.49(d, 1H), 3.48-3.23(m,4H), 3.08(m, 1H), 2.56(dd, 2H), 1.78-1.72(m, 2H), 1.38(d, 3H), 1.01(t,3H) 119 (R)-N-(2-methylpiperazin-1-yl)-6- ¹H-NMR(400 MHz, CDCl₃) δ8.35(s, 1H), 8.01(brs, propyl-N-[3- 1H), 7.43-7.36(m, 2H), 7.25(d, 1H),5.92(s, 1H), (trifluoromethyl)phenyl]pyrimidin- 4.56(brs, 1H), 4.10(d,1H), 3.28-3.19(m, 2H), 3.08- 2-amine 3.00(m, 2H), 2.85(m, 1H), 2.53(dd,2H), 1.81- 1.72(m, 2H), 1.37(d, 3H), 1.00(t, 3H)

TABLE 1-13 Example Compound NMR Spectrum 120(R)-N-(2-methylpiperazin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ 9.13(s, 1H),7.76(d, N-(3-nitrophenyl)-6- 1H), 7.67(d, 1H), 7.45(dd, 1H), 6.19(d,1H), propylpyrimidin-2-amine 4.81(brd, 1H), 4.33(d, 1H), 3.30-3.23(m,2H), 3.17(d, 2H), 2.97(m, 1H), 2.53(dd, 2H), 1.79- 1.73(m, 2H), 1.35(d,3H), 0.99(t, 3H) 121 (R)-N-(4-fluoro-3-nitrophenyl)-4- ¹H-NMR(400 MHz,CD₃OD) δ 8.96(dd, 1H), 7.64(dd, (2-methylpiperazin-1-yl)-6- 1H),7.28(dd, 1H), 6.17(s, 1H), 4.75(brs, 1H), propylpyrimidin-2-amine4.29(d, 1H), 3.27-3.21(m, 2H), 3.13(d, 2H), 2.93(m, 1H), 2.51(dd, 2H),1.78-1.70(m, 2H), 1.33(d, 3H), 0.98(t, 3H) 122(R)-N-(4-methyl-3-nitrophenyl)- ¹H-NMR(400 MHz, CD₃OD) δ 8.83(d, 1H),7.49(dd, 4-(2-methylpiperazin-1-yl)-6- 1H), 7.27(d, 1H), 6.15(s, 1H),4.77-4.75(m, 1H), propylpyrimidin-2-amine 4.29(d, 1H), 3.26-3.19(m, 2H),3.12(d, 2H), 2.92(m, 1H), 2.50(dd, 2H), 2.49(s, 3H), 1.77-1.70(m, 2H),1.32(d, 3H), 0.98(t, 3H) 123 (R)-4-fluoro-N¹-[4-(2- ¹H-NMR(400 MHz,CD₃OD) δ 7.07(dd, 1H), 6.89(dd, methylpiperazin-1-yl)-6- 1H),6.79-6.77(m, 1H), 6.23(s, 1H), 4.87(brs, 1H),propylpyrimidin-2-yl]benzene- 4.47(d, 1H), 3.44-3.25(m, 4H), 3.10(m,1H), 1,3-diamine 2.53(dd, 2H), 1.76-1.70(m, 2H), 1.36(d, 3H), 0.99(t,3H) 124 (R)-N¹-[4-(2-methylpiperazin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.83(d,1H), 7.32(dd, yl)-6-propylpyrimidin-2-yl]-3- 1H), 6.82(d, 1H), 6.16(s,1H), 4.87(brs, 1H), (trifluoromethyl)benzene-1,4- 4.40(dd, 1H),3.39-3.21(m, 4H), 3.06(m, 1H), diamine 2.50(dd, 2H), 1.76-1.70(m, 2H),1.34(d, 3H), 0.98(t, 3H) 125 (R)-2-fluoro-5-[4-(2- ¹H-NMR(400 MHz,CD₃OD) δ 8.26-8.24(m, 1H), methylpiperazin-1-yl)-6- 7.82-7.78(m, 1H),7.23(dd, 1H), 6.13(s, 1H), propylpyrimidin-2- 4.59(brs, 1H), 4.16(d,1H), 3.18-3.12(m, 2H), 3.04- ylamino]benzonitrile 2.98(m, 2H),2.85-2.79(m, 1H), 2.50(dd, 2H), 1.76- 1.69(m, 2H), 1.30(d, 3H), 0.98(t,3H) 126 (R)-2-methyl-5-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 8.19(d, 1H),7.63(dd, methylpiperazin-1-yl)-6- 1H), 7.27(d, 1H), 6.15(s, 1H),4.74-4.73(m, 1H), propylpyrimidin-2- 4.27(d, 1H), 3.28-3.20(m, 2H),3.15(d, 2H), 2.98- ylamino]benzonitrile 2.92(m, 1H), 2.51(dd, 2H),2.45(s, 3H), 1.77- 1.71(m, 2H), 1.34(d, 3H), 0.98(t, 3H) 127(R)-2-amino-5-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 7.70(s, 1H), 7.40(d,methylpiperazin-1-yl)-6- 1H), 6.80(d, 1H), 6.19(s, 1H), 4.88(brs, 1H),4.40(d, propylpyrimidin-2- 1H), 3.43-3.24(m, 4H), 3.10(m, 1H), 2.51(dd,2H), ylamino]benzonitrile 1.76-1.68(m, 2H), 1.36(d, 3H), 0.99(t, 3H) 128(R)-N¹-[4-(2-methylpiperazin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.79(s, 1H),7.34(d, yl)-6-propylpyrimidin-2-yl]-3- 1H), 6.92(d, 1H), 6.14(s, 1H),4.88(brs, 1H), 4.44(d, nitrobenzene-1,4-diamine 1H), 3.40-3.24(m, 4H),3.09(m, 1H), 2.50(dd, 2H), 1.76-1.71(m, 2H), 1.36(d, 3H), 0.98(t, 3H)129 (R)-3-amino-5-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 7.45(s, 1H), 7.12(s,methylpiperazin-1-yl)-6- 1H), 6.56(s, 1H), 6.18(s, 1H), 4.84(brd, 1H),4.36(d, propylpyrimidin-2- 1H), 3.39-3.20(m, 4H), 3.04(m, 1H), 2.52(dd,2H), ylamino]benzonitrile 1.77-1.69(m, 2H), 1.36(d, 3H), 0.98(t, 3H)

TABLE 1-14 Example Compound NMR Spectrum 130(R)-3-[4-(2-methylpiperazin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.43(s, 1H),7.61(d, yl)-6-propylpyrimidin-2- 1H), 7.45(d, 1H), 7.36(dd, 1H), 6.22(s,1H), ylamino]benzamide 4.96(brs, 1H), 4.52(d, 1H), 3.47-3.31(m, 4H),3.14(dd, 1H), 2.53(dd, 2H), 1.78-1.72(m, 2H), 1.37(d, 3H), 0.99(t, 3H)131 3-{4-[2-(2-hydroxyethyl)piperidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.19(s,1H), 7.64(d, 1-yl]-6-propylpyrimidin-2- 1H), 7.36(t, 1H), 7.26(m, 1H),6.05(s, 1H), 4.92(br, ylamino}benzonitrile 1H), 4.01(br, 1H), 3.65(m,1H), 3.46(m, 1H), 3.02(m, 1H), 2.52(t, 2H), 2.10-2.05(m, 2H), 1.81-1.72(m, 8H), 1.53(m, 1H), 0.99(t, 3H) 132 2-{1-[2-(4-chloro-3-¹H-NMR(400 MHz, CDCl₃) δ 13.39(br, 1H), 11.20(d, nitrophenylamino)-6-1H), 8.78(s, 1H), 8.59(s, 1H), 7.67(m, 1H), 7.47(m,propylpyrimidin-4-yl]piperidin-2- 3H), 7.24(m, 1H), 6.36(s, 1H), 5.98(s,1H), 5.41(br, yl}ethanol hydrochloride 1H), 4.90-4.87(br, 1H), 4.47(br,1H), 3.83(br, 1H), 3.78(m, 1H), 3.57(m, 2H), 3.31(m, 1H), 3.03(m, 1H),2.60(m, 4H), 2.09(m, 2H), 2.00-1.84(m, 16H), 1.60(br, 2H), 0.99(m, 6H)133 2-(1-{2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 13.60(s, 1H), 13.35(s,(methylthio)phenylamino]-6- 1H), 10.45(s, 1H), 10.41(s, 1H), 7.61(s,1H), 7.48(s, propylpyrimidin-4-yl}piperidin-2- 1H), 7.34-7.21(m, 4H),7.00(m, 2H), 6.23(s, 1H), yl)ethanol hydrochloride 5.92(s, 1H), 5.24(br,1H), 4.88(d, 1H), 4.45(br, 1H), 3.82-3.75(br, 2H), 3.58(br, 1H),3.47(br, 1H), 3.24(t, 1H), 2.95(t, 1H), 2.62(m, 4H), 2.47(s, 6H),2.33(br, 2H), 2.08(br, 2H), 1.85(m, 16H), 1.50(br, 2H), 0.95(m, 6H) 1342-{1-[2-(1-ethyl-1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.89(brs, 1H),7.50(d, ylamino)-6-propylpyrimidin-4- 1H), 7.04-7.00(m, 2H), 6.42(m,1H), 5.93(s, 1H), yl]piperidin-2-yl}ethanol 4.92(br, 1H), 4.14(m, 2H),3.50(m, 1H), 3.33(br, 1H), 2.97(m, 1H), 2.52(m, 2H), 2.09-2.04(m, 2H),1.82-1.71(m, 8H), 1.55(t, 3H), 1.28(t, 3H) 1352-{1-[2-(1H-indol-5-ylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.59(s, 1H),7.68(s, propylpyrimidin-4-yl]piperidin-2- 1H), 7.22(m, 2H),7.20-6.98(br, 1H), 6.99(s, 1H), yl}ethanol 6.40(s, 1H), 5.87(s, 1H),4.98(br, 1H), 3.42(m, 1H), 3.23(m, 1H), 2.93(m, 1H), 2.47(m, 2H),2.02(m, 1H), 1.82-1.62(m, 8H), 1.56(m, 2H), 1.01(t, 3H) 1362-(1-{6-propyl-2-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.09(br, 1H), 7.51(d,(trifluoromethyl)-1H- 1H), 7.45(br, 1H), 7.13(d, 1H), 6.81(brs, 1H),benzo[d]imidazol-6- 6.75(d, 1H), 5.87(s, 1H), 5.08(br, 1H), 3.81(br,2H), ylamino]pyrimidin-4-yl}piperidin- 3.67-3.51(m, 2H), 3.03(m, 1H),2.33(m, 2H), 2-yl)ethanol 2.06(m, 1H), 1.75-1.61(m, 7H), 1.52(m, 1H),0.93(t, 3H) 137 2-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.43(d, 2H),6.87(d, methoxyphenylamino)-6- 2H), 5.97(br, 1H), 4.87(br, 1H), 3.80(s,3H), 3.57(br, propylpyrimidin-4-yl]piperidin-2- 1H), 3.38(m, 1H),2.99(m, 1H), 2.53(m, 2H), 2.05(m, yl}ethanol 1H), 1.80-1.70(m, 8H),1.53(m, 1H), 1.00(t, 3H) 138 2-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ7.42(s, 1H), 7.17(t, 1H), methoxyphenylamino)-6- 6.95(d, 1H), 6.89(br,1H), 6.54(d, 1H), 5.93(s, 1H), propylpyrimidin-4-yl]piperidin-2-4.97(br, 1H), 3.95(br, 1H), 3.90(s, 3H), 3.56(m, 1H), yl}ethanol 3.35(m,1H), 2.95(t, 1H), 2.47(m, 2H), 2.06(m, 1H), 1.79-1.63(m, 8H), 1.54(m,1H), 1.00(t, 3H)

TABLE 1-15 Example Compound NMR Spectrum 139 2-{1-[2-(5-methoxy-2-¹H-NMR(400 MHz, CDCl₃) δ 7.70(s, 1H), 7.05(d, methylphenylamino)-6- 1H),6.55(d, 1H), 5.94(s, 1H), 4.94(br, 1H), 4.09(br,propylpyrimidin-4-yl)piperidin-2- 1H), 3.79(s, 3H), 3.52(m, 1H), 3.34(m,1H), 2.96(t, yl}ethanol 1H), 2.49(m, 2H), 2.26(s, 3H), 2.04(m, 1H),1.80- 1.64(m, 8H), 1.52(m, 1H), 1.01(t, 3H) 140 2-{1-[2-(3-chloro-4-¹H-NMR(400 MHz, CDCl₃) δ 7.77(s, 1H), 7.20(d, methylphenylamino}-6- 1H),7.10(d, 1H), 5.95(s, 1H), 4.91(br, 1H), 3.96(br,propylpyrimidin-4-yl]piperidin-2- 1H), 3.58(m, 1H), 3.38(m, 1H), 2.97(t,1H), 2.48(m, yl}ethanol 2H), 2.30(s, 3H), 2.07(m, 1H), 1.77-1.71(m, 8H),1.52(m, 1H), 0.98(t, 3H) 141 2-{1-[2-(3-nitrophenylamino)-6- ¹H-NMR(400MHz, CDCl₃) δ 8.96(s, 1H), 7.77(d, propylpyrimidin-4-yl]piperidin-2-1H), 7.54(d, 1H), 7.37(m, 2H), 6.02(s, 1H), 4.99(br, yl}ethanol 1H),3.96(br, 1H), 3.60(m, 1H), 3.42(m, 1H), 2.93(t, 1H), 2.50(m, 2H),2.07(m, 1H), 1.81-1.68(m, 8H), 1.54(m, 1H), 0.99(t, 3H) 1422-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.80(d, 1H), 7.76(br,nitrophenylamino)-6- 1H), 7.52(m, 1H), 7.15(t, 1H), 6.03(s, 1H),4.97(br, propylpyrimidin-4-yl]piperidin-2- 1H), 3.97(br, 1H), 3.60(m,1H), 3.41(m, 1H), 2.99(t, yl}ethanol 1H), 2.50(m, 2H), 2.09(m, 1H),1.80-1.71(m, 8H), 1.52(m, 1H), 0.99(t, 3H) 1432-{1-[2-(2,3-dimethylbenzofuran- ¹H-NMR(400 MHz, CDCl₃) δ 7.74(s, 1H),7.26(d, 5-ylamino)-6-propylpyrimidin-4- 1H), 7.15(d, 1H), 6.78(br, 1H),5.89(s, 1H), 4.99(br, yl]piperidin-2-yl}ethanol 1H), 3.86(br, 1H),3.47(m, 1H), 3.28(m, 1H), 2.94(m, 1H), 2.47(m, 2H), 2.35(s, 3H), 2.19(s,3H), 2.11-2.05(br, 1H), 1.82-1.57(m, 9H), 1.00(t, 3H) 1442-{1-[6-propyl-2-(quinolin-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.75(d, 1H),8.28(d, ylamino)pyrimidin-4-yl]piperidin- 1H), 8.04(d, 1H), 8.00(d, 1H),7.70(dd, 1H), 7.33(m, 2-yl}ethanol 1H), 7.07(br, 1H), 6.00(s, 1H),5.01(br, 1H), 3.95(br, 1H), 3.59(m, 1H), 3.40(m, 1H), 2.96(t, 1H),2.53(m, 2H), 2.07(m, 1H), 1.84-1.68(m, 8H), 1.57(m, 1H), 1.01(t, 3H) 1452-{1-[2-(3-chlorophenylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.85(s, 1H),7.27(d, propylpyrimidin-4-yl]piperidin-2- 1H), 7.18(t, 1H), 6.94(d, 1H),6.89(br, 1H), 5.95(s, yl}ethanol 1H), 4.93(br, 1H), 3.90(br, 1H),3.61(m, 1H), 3.39(t, 1H), 2.96(t, 1H), 2.48(m, 2H), 2.07(m, 1H), 1.79-1.65(m, 8H), 1.52(m, 1H), 0.97(t, 3H) 1467-{4-[2-(2-hydroxyethyl)piperidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.01(s, 1H),7.85(br, 1-yl]-6-propylpyrimidin-2- 1H), 7.46(d, 1H), 7.22(m, 1H),6.12(s, 1H), 6.02(s, ylamino}-4-methyl-2H-chromen- 1H), 4.95(br, 1H),3.95(br, 1H), 3.63(m, 1H), 2-one 3.44(m, 1H), 2.97(t, 1H), 2.53(m, 2H),2.39(s, 3H), 2.08(m, 1H), 1.79-1.69(m, 8H), 1.56(m, 1H), 0.99(t, 3H) 1472-{1-[6-propyl-2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.20(s, 1H), 7.45(d,trifluoromethylphenylamino)pyrimidin- 1H), 7.36(t, 1H), 7.21(d, 1H),6.97(br, 1H), 5.97(s, 4-yl]piperidin-2-yl}ethanol 1H), 4.94(br, 1H),4.13(br, 1H), 3.56(m, 1H), 3.38(m, 1H), 2.99(m, 1H), 2.50(t, 1H),2.08(m, 2H), 1.80-1.63(m, 8H), 1.54(m, 1H), 0.99(t, 3H)

TABLE 1-16 Example Compound NMR Spectrum 1482-{1-[6-propyl-2-(quinolin-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.96(s, 1H),8.58(d, ylamino)pyrimidin-4-yl]piperidin- 1H), 8.00(d, 1H), 7.71(d, 1H),7.55-7.51(m, 2H), 2-yl}ethanol 7.47(br, 1H), 6.02(s, 1H), 5.00(br, 1H),3.95(br, 1H), 3.63(m, 1H), 3.48(m, 1H), 2.97(t, 1H), 2.52(m, 2H),2.08(m, 1H), 1.81-1.65(m, 8H), 1.54(m, 1H), 1.99(t, 3H) 1493-{4-[2-(2-hydroxyethyl)piperidin- ¹H-NMR(400 MHz, CDCl₃) δ 13.60(br,1H), 11.06(d, 1-yl]-6-propylpyrimidin-2- 1H), 8.16(br, 2H), 7.70(m, 2H),7.43(m, 4H), 6.03(s, ylamino}benzonitrile 2H), 5.27(m, 1H), 4.82(m, 1H),4.29(m, 1H), 4.08(m, hydrochloride 2H), 3.97(m, 2H), 3.87(m, 1H),3.31(m, 1H), 3.06(m, 1H), 2.65(m, 4H), 2.19(m, 2H), 2.00-1.57(m, 16H),1.52(m, 2H), 1.00(m, 6H) 150 (S)-5-[4-(3-aminopiperidin-1-yl)-¹H-NMR(400 MHz, CD₃OD) δ 7.92-7.83(d, 1H),6-propylpyrimidin-2-ylamino]-2- 7.72-7.64(d, 1H), 7.49(m, 1H), 6.59(m,1H), 4.59- methylbenzonitrile 3.99(br, 2H), 3.65-3.60(m, 3H), 2.68(m,2H), 2.53(s, dihydrochloride 3H), 2.20(m, 1H), 1.95(br, 1H), 1.80(m,4H), 1.06(t, 3H) 151 (S)-4-(3-aminopiperidin-1-yl)-N- ¹H-NMR(400 MHz,CD₃OD) δ 8.80(s, 1H), 8.07(d, (3-nitrophenyl)-6- 1H), 7.75(d, 1H),7.67(m, 1H), 6.64(br, 1H), 4.47- propylpyrimidin-2-amine 4.03(br, 2H),3.50(m, 3H), 2.70(m, 2H), 2.22(m, dihydrochloride 1H), 1.99(m, 1H),1.82(m, 4H), 1.07(t, 3H) 152 (S)-3-[4-(3-aminopiperidin-1-yl)-¹H-NMR(400 MHz, CD₃OD) δ 7.99-7.94(br, 1H), 6-propylpyrimidin-2-7.81(br, 1H), 7.57(m, 2H), 6.62(br, 1H), 4.82- ylamino]benzonitrile4.18(br, 2H), 3.57(m, 2H), 3.48(br, 1H), 2.69(m, dihydrochloride 2H),2.20(br, 1H), 1.96(br, 1H), 1.79(m, 4H), 1.06(t, 3H) 153(R)-5-[4-(3-aminopiperidin-1-yl)- ¹H-NMR(400 MHz, CDCl₃) δ 8.25(d, 1H),7.42(d, H), 6-propylpyrimidin-2-ylamino]-2- 7.40(br, 1H), 7.17(d, 1H),5.96(s, 1H), 4.25(m, 1H), methylbenzonitrile 4.05(m, 1H), 3.05(m, 1H),2.87(m, 1H), 2.78(m, 1H), 2.47-2.45(m, 5H), 2.02(br, 3H), 1.84(m, 1H),1.74(m, 2H), 1.68(m, 1H), 1.38(m, 1H), 1.00(t, 3H) 154(S)-5-{4-[3-(butylamino)piperidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.11(s, 1H),7.51(d, 1-yl]-6-propylpyrimidin-2- 1H), 7.18(d, 1H), 6.94(br, 1H),5.96(s, 1H), 4.29(br, ylamino}-2-methylbenzonitrile 1H), 4.05(br, 1H),3.05(t, 1H), 2.87(m, 1H), 2.69(m, 3H), 2.49-2.45(m, 3 + 2H), 2.01(m,1H), 1.81(m, 1H), 1.73(m, 2H), 1.60(m, 3H), 1.46(m, 2H), 1.35(m, 2H),0.95(t, 3H), 0.85(t, 3H) 155 (S)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.11(s, 1H), 7.53(dd, (pentylamino)piperidin-1-yl]-6- 1H), 7.18(d, 1H),7.00(br, 1H), 5.96(s, 1H), 4.25(m, propylpyrimidin-2-ylamino}-2- 1H),4.05(m, 1H), 2.90(m, 1H), 2.72(m, 1H), 2.68(m, methylbenzonitrile 3H),2.48(m, 5H), 2.01(m, 1H), 1.83(m, 1H), 1.77(m, 3H), 1.69(m, 2H), 1.53(m,3H), 1.31(m, 4H), 0.98(t, 3H), 0.87(t, 3H) 156 (S)-5-{4-[3- ¹H-NMR(400MHz, CDCl₃) δ 8.09(s, 1H), 7.53(d, (isobutylamino)piperidin-1-yl]-6-1H), 7.18(d, 1H), 7.06(br, 1H), 5.96(s, 1H), 4.28(m,propylpyrimidin-2-ylamino}-2- 1H), 4.05(m, 1H), 3.07(m, 1H), 2.87(m,1H), 2.63(m, methylbenzonitrile 1H), 2.59-2.44(m, 7H), 2.02(m, 1H),1.83(m, 1H), 1.77(m, 5H), 1.55(m, 1H), 1.46(m, 1H), 1.00(t, 3H), 0.90(m,6H)

TABLE 1-17 Example Compound NMR Spectrum 157 (S)-5-{4-[3- ¹H-NMR(400MHz, CDCl₃) δ 8.11(d, 1H), 7.51(dd, (isopentylamino)piperidin-1-yl]-6-1H), 7.18(d, 1H), 7.03(br, 1H), 5.96(s, 1H), 4.27(m,propylpyrimidin-2-ylamino}-2- 1H), 4.05(m, 1H), 3.08(m, 1H), 2.91(m,1H), 2.69(m, methylbenzonitrile 3H), 2.47(m, 5H), 2.02(m, 1H), 1.83(m,1H), 1.79(m, 4H), 1.58(m, 3H), 1.45(m, 3H), 0.95(t, 3H), 0.85(m, 6H) 158(S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.07(s, 1H), 7.55(d,(neopentylamino)piperidin-1-yl]- 1H), 7.18(d, 1H), 6.95(br, 1H), 5.95(s,1H), 4.24(m, 6-propylpyrimidin-2- 1H), 4.04(m, 1H), 3.10(m, 1H), 2.86(m,1H), 2.57(m, ylamino}benzonitrile 1H), 2.47(m, 5H), 2.01(m, 1H), 1.83(m,1H), 1.77(m, 2H), 1.67(m, 3H), 1.54(m, 2H), 1.00(t, 3H), 0.90(s, 9H) 159(S)-5-(4-{3-[(1H-pyrrol-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.93(br, 1H),8.32(s, yl)methylamino]piperidin-1-yl}-6- 1H), 7.33(d, 1H), 7.17(d, 1H),6.73(s, 1H), 6.11(s, propylpyrimidin-2-ylamino)-2- 1H), 6.02(s, 1H),5.91(s, 1H), 4.32(br, 1H), 3.91(m, methylbenzonitrile 3H), 3.08(m, 1H),2.96(m, 1H), 2.72(m, 1H), 2.48- 2.45(m, 5H), 2.05(m, 1H), 1.83(m, 1H),1.72(m, 3H), 1.58(m, 1H), 1.46(m, 1H), 0.95(m, 3H) 160(S)-2-methyl-5-(4-propyl-6-{3- ¹H-NMR(400 MHz, CDCl₃) δ 8.10(s, 1H),7.51(dd, [(thiophen-2- 1H), 7.20-7.16(m, 2H), 7.00(br, 1H), 6.94-6.91(m,ylmethyl)amino]piperidin-1- 2H), 5.92(s, 1H), 4.25(m, 1H), 4.07(m, 2H),4.04(m, yl}pyrimidin-2- 1H), 3.08(m, 1H), 2.99(m, 1H), 2.72(m, 1H),2.46(m, ylamino)benzonitrile 5H), 1.99(m, 1H), 1.80(m, 1H), 1.71(m, 2H),1.58- 1.45(m, 3H), 0.98(t, 3H) 161 (S)-5-(4-{3-[(4,5-dimethylfuran-2-¹H-NMR(400 MHz, CDCl₃) δ 8.09(s, 1H), 7.52(m,ylmethyl)amino]piperidin-1-yl}-6- 1H), 7.17(d, 1H), 6.97(br, 1H),5.93(s, 1H), 5.92(s, propylpyrimidin-2-ylamino)-2- 1H), 4.20-4.09(m,2H), 3.77(s, 2H), 3.02(m, 1H), methylbenzonitrile 2.90(m, 1H), 2.66(m,5H), 2.49(s, 3H), 2.01(m, 1H), 1.89(s, 3H), 1.77(m, 1H), 1.69(m, 3H),1.55(m, 1H), 1.47(m, 1H), 0.98(t, 3H) 162 (S)-2-methyl-5-{4-[3-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.15(s, 1H), 7.49(d,methylthiopropylamino)piperidin- 1H), 7.18(d, 1H), 6.93(br, 1H), 5.96(s,1H), 4.30(m, 1-yl]-6-propylpyrimidin-2- 1H), 4.05(m, 1H), 3.09(m, 1H),2.81(m, 1H), 2.78(m, ylamino}benzonitrile 2H), 2.67(m, 1H), 2.55(t, 2H),2.47(m, 5H), 2.09(s, 3H), 2.01(m, 1H), 1.79(m, 2H), 1.69(m, 3H), 1.61(m,1H), 1.41(m, 1H), 0.98(t, 3H) 163 (S)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.10(d, 1H), 7.53(dd, (cyclopropylmethylamino)piperidin- 1H), 7.18(d,1H), 6.90(br, 1H), 5.96(s, 1H), 4.30(m, 1-yl]-6-propylpyrimidin-2- 1H),4.01(m, 1H), 3.09(m, 1H), 2.96(m, 1H), 2.72(m,ylamino}-2-methylbenzonitrile 1H), 2.59(m, 1H), 2.52(m, 1H), 2.49(m,5H), 2.01(m, 2H), 1.82(m, 1H), 1.75(m, 2H), 1.59(m, 1H), 1.48(m, 1H),0.98(t, 3H), 0.48(m, 2H), 0.13(m, 2H) 164 (S)-5-{4-[3-(4- ¹H-NMR(400MHz, CDCl₃) δ 8.02(s, 1H), 7.48(d, hydroxybenzylamino)piperidin-1- 1H),7.11(d, 1H), 7.00(d, 2H), 6.70(d, 2H), 5.91(s,yl]-6-propylpyrimidin-2-ylamino}- 1H), 4.24(br, 1H), 3.95(br, 1H),3.75(m, 2H), 2-methylbenzonitrile 3.16(m, 1H), 3.07(m, 1H), 2.71(m, 1H),2.49(m, 2H), 2.44(s, 3H), 1.99(m, 1H), 1.79(m, 1H), 1.74(m, 2H), 1.50(m,3H), 0.97(t, 3H)

TABLE 1-18 Example Compound NMR Spectrum 165 (S)-5-[4-(3- ¹H-NMR(400MHz, CDCl₃) δ 8.09(d, 1H), 7.52(dd, diethylaminopiperidin-1-yl)-6- 1H),7.18(d, 1H), 6.87(br, 1H), 5.96(s, 1H), 4.44-propylpyrimidin-2-ylamino]-2- 4.31(br, 2H), 2.75(m, 2H), 2.65(m, 4H),2.47(m, methylbenzonitrile 4H), 1.99(m, 1H), 1.84(m, 1H), 1.75(m, 4H),1.53(m, 2H), 1.05(t, 6H), 0.98(t, 3H) 166 (S)-5-(4-{3- ¹H-NMR(400 MHz,CDCl₃) δ 8.17(d, 1H), 7.55(dd, [bis(cyclopropylmethyl)amino]piperidin-1H), 7.24(d, 1H), 6.99(br, 1H), 6.03(s, 1H), 4.49-1-yl}-6-propylpyrimidin-2- 4.04(br, 2H), 2.99(m, 1H), 2.83(m, 2H),2.64(m, ylamino)-2-methylbenzonitrile 3H), 2.53(m, 4H), 2.04(m, 1H),1.92(m, 1H), 1.79(m, 2H), 1.59(m, 2H), 1.06(t, 3H), 0.93(m, 2H), 0.55(m,4H), 0.20(m, 4H) 167 (R)-5-(4-{3- ¹H-NMR(400 MHz, CDCl₃) δ 8.17(d, 1H),7.55(dd, [bis(cyclopropylmethyl)amino]piperidin- 1H), 7.39(br, 1H),7.24(d, 1H), 6.03(s, 1H), 4.49- 1-yl}-6-propylpyrimidin-2- 4.04(br, 2H),2.99(m, 1H), 2.83(m, 2H), 2.64(m, ylamino)-2-methylbenzonitrile 3H),2.53(m, 4H), 2.04(m, 1H), 1.92(m, 1H), 1.79(m, 2H), 1.59(m, 2H), 1.06(t,3H), 0.93(m, 2H), 0.55(m, 4H), 0.20(m, 4H) 1684-ethyl-N-(4-fluorophenyl)-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.34(m, 2H),7.17(m, (piperidin-1-yl)pyrimidin-2-amine 2H), 6.10(s, 1H), 3.61(m, 4H),2.58(m, 2H), 1.61(m, 6H), 1.21(m, 3H) 169 4-ethyl-N-(4-fluorophenyl)-6-¹H-NMR(400 MHz, CD₃OD) δ 7.43(m, 2H), 7.17(m, (octahydroquinolin-1(2H)-2H), 6.24(s, 1H), 4.15(m, 1H), 3.38(m, 1H), 2.58(m, yl)pyrimidin-2-amine2H), 2.10(m, 1H), 1.91-1.66(m, 7H), 1.39(m, 3H), 1.27-1.13(m, 6H) 1704-ethyl-6-(2-ethylpiperidin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ 7.42(m, 2H),7.18(m, N-(4-fluorophenyl)pyrimidin-2- 2H), 6.38(s, 1H), 4.51-4.27(m,2H), 3.08(m, 1H), amine 2.58(m, 2H), 1.88-1.66(m, 7H), 1.51(m, 1H),1.25(m, 3H), 0.99(m, 3H) 171 2-{1-[6-ethyl-2-(4- ¹H-NMR(400 MHz, CD₃OD)δ 7.43(m, 2H), 7.17(m, fluorophenylamino)pyrimidin-4- 2H), 6.41(s, 1H),3.59-3.49(m, 2H), 3.12(m, 1H), yl]piperidin-2-yl}ethanol 2.58(m, 2H),2.05(m, 1H), 1.86-1.69(m, 8H), 1.53(m, 1H), 1.23(m, 3H) 1724-ethyl-N-(4-fluorophenyl)-6- ¹H-NMR(400 MHz, CD₃OD) δ 7.43(m, 2H),7.22(t, morpholinopyrimidin-2-amine 2H), 6.43(s, 1H), 3.76-3.70(m, 8H),2.62(q, 2H), 1.25(t, 3H) 173 N-[4-(piperidin-1-yl)-6- ¹H-NMR(400 MHz,CDCl₃) δ 13.20(s, 1H), 10.26(s, propylpyrimidin-2-yl]-1H-indol-6- 1H),8.78(s, 1H), 7.68(s, 1H), 7.52(d, 1H), 7.29(d, amine hydrochloride 1H),7.22(s, 1H), 6.49(s, 1H), 5.77(s, 1H), 3.88(m, 2H), 3.48(m, 2H), 2.55(t,2H), 1.82(m, 2H), 1.73(m, 2H), 1.66(m, 4H), 1.00(t, 3H) 1742-{1-[2-(4-methyl-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.73(s, 1H), 7.70(brs,nitrophenylamino)-6- NH), 7.38(d, 1H), 7.19(d, 1H), 6.01(s, 1H),5.08(brs, propylpyrimidin-4-yl]piperidin-2- 1H), 3.99(brs, 1H), 3.48(m,1H), 3.37(m, 1H), yl}ethanol 2.96(m, 1H), 2.54-2.47(m, 5H), 2.08(m, 1H),1.80- 1.70(m, 8H), 1.54(m, 1H), 0.99(t, 3H)

TABLE 1-19 Example Compound NMR Spectrum 175 2-{1-[2-(4-amino-3-¹H-NMR(400 MHz, CDCl₃) δ 7.87(s, 1H), 7.27(d,trifluoromethylphenylamino)-6- 1H), 6.71(d, 1H), 5.93(s, 1H), 4.87(brs,1H), 4.04(s, propylpyrimidin-4-yl]piperidin-2- 3H), 3.53(m, 1H), 3.33(m,1H), 2.95(m, 1H), 2.47(t, yl}ethanol 2H), 2.05(m, 1H), 1.73(m, 8H),1.51(m, 1H), 0.85(t, 3H) 176 2-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CDCl₃)δ 8.67(s, 1H), 7.26(d, nitrophenylamino)-6- 1H), 6.85(brs, 1H), 6.74(d,1H), 5.93(s, 1H + 2H), propylpyrimidin-4-yl]piperidin-2- 5.08(brs, 1H),3.89(brs, 1H), 3.56(m, 1H), 3.33(m, yl}ethanol 1H), 2.94(m, 1H), 2.46(t,2H), 2.04(m, 1H), 1.82- 1.66(m, 8H), 1.54(m, 1H), 0.99(t, 3H) 1775-{4-[2-(2-hydroxyethyl)piperidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.10(s, 1H),7.45(d, 1-yl]-6-propylpyrimidin-2- 1H), 7.18(d, 1H), 7.07(brs, 1H),5.97(s, 1H), ylamino}-2-methylbenzonitrile 4.93(brs, 1H), 3.90(brs, 1H),3.59(m, 1H), 3.35(m, 1H), 2.97(m, 1H), 2.47(m, 3H + 2H), 2.07(m, 1H),1.74-1.69(m, 8H), 1.51(m, 1H), 0.99(t, 3H) 178 2-fluoro-5-{4-[2-(2-¹H-NMR(400 MHz, CDCl₃) δ 8.14(m, 1H), 7.66(m,hydroxyethyl)piperidin-1-yl]-6- 1H), 7.12(m, 1H), 6.05(s, 1H), 4.92(brs,1H), propylpyrimidin-2- 4.00(brs, 1H), 3.67(m, 1H), 3.48(m, 1H), 3.03(m,ylamino}benzonitrile 1H), 2.53(t, 2H), 2.07(m, 1H), 1.73(m, 8H), 1.53(m,1H), 1.00(t, 3H) 179 2-amino-5-{4-[2-(2- ¹H-NMR(400 MHz, CDCl₃) δ7.77(s, 1H), 7.32(d, hydroxyethyl)piperidin-1-yl]-6- 1H), 7.04(brs, 1H),6.70(d, 1H), 5.91(s, 1H), propylpyrimidin-2- 4.89(brs, 1H), 4.24(s, 2H),3.86(brs, 1H), 3.58(m, ylamino}benzonitrile 1H), 3.33(m, 1H), 2.95(m,1H), 2.45(t, 2H), 2.05(t, 1H), 1.72(m, 8H), 1.50(m, 1H), 0.85(t, 3H) 1802-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.02(s, 1H), 6.94(d,methylphenylamino)-6- 1H), 6.79(d, 1H), 5.88(s, 1H), 5.00(brs, 1H),propylpyrimidin-4-yl]piperidin-2- 3.84(brs, 1H), 3.55(m, 1H), 3.35(m,1H), 2.95(m, yl}ethanol 1H), 2.46(t, 2H), 2.11(s, 1H), 2.06(m, 2H),1.71(m, 8H), 1.52(m, 1H), 0.85(t, 3H) 181 2-{1-[2-(3-amino-4- ¹H-NMR(400MHz, CDCl₃) δ 7.15(d, 1H), 6.98(brs, fluorophenylamino)-6- 1H), 6.89(m,1H), 6.74(m, 1H), 5.90(s, 1H), propylpyrimidin-4-yl]piperidin-2-4.96(brs, 1H), 3.83(brs, 1H), 3.74(s, 2H), 3.55(m, yl}ethanol 1H),3.36(m, 1H), 2.96(m, 1H), 2.46(t, 2H), 2.06(m, 1H), 1.71(m, 8H), 1.53(m,1H), 0.88(t, 3H) 182 2-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ7.25(d, 1H), 7.10(d, chlorophenylamino)-6- 1H), 6.85(brs, 1H), 6.76(d,1H), 5.91(s, 1H), propylpyrimidin-4-yl]piperidin-2- 4.99(brs, 1H),4.06(s, 2H), 3.84(brs, 1H), 3.58(m, yl}ethanol 1H), 3.39(m, 1H), 2.96(m,1H), 2.46(t, 2H), 2.08(m, 1H), 1.71(m, 8H), 1.51(m, 1H), 0.98(t, 3H) 1832-{1-[2-(indolin-6-ylamino)-6- ¹H-NMR(400 MHz, CDCl₃) δ 7.01(m, 3H),6.76(d, propylpyrimidin-4-yl]piperidin-2- 1H), 5.88(s, 1H), 4.96(brs,1H), 3.85(brs, 1H), yl}ethanol 3.54(m, 3H), 3.35(m, 1H), 2.97(m, 3H),2.45(t, 2H), 3.01(m, 1H), 1.71(m, 8H), 1.51(m, 1H), 0.98(t, 3H) 184(S)-2-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.73(s, 1H), 8.21(brs,nitrophenylamino)-6- 1H), 7.47(d, 1H), 7.36(d, 1H), 6.02(s, 1H),4.94(brs, propylpyrimidin-4-yl]piperidin-2- 1H), 3.95(s, 1H), 3.65(m,1H), 3.44(m, 1H), 2.99(t, yl}ethanol 1H), 2.49(t, 2H), 2.09(m, 1H),1.75-1.51(m, 6H), 1.51(m, 1H), 0.98(t, 3H)

TABLE 1-20 Example Compound NMR Spectrum 185 (S)-2-{1-[2-(4-amino-3-¹H-NMR(400 MHz, CDCl₃) δ 8.70(s, 1H), 7.30(m, nitrophenylamino)-6- 1H),6.78(d, 1H), 6.15(s, 2H), 6.00(s, 1H), 4.97(brs,propylpyrimidin-4-yl]piperidin-2- 1H), 4.06(brs, 1H), 3.58(m, 1H),3.43(m, 1H), 3.03(t, yl}ethanol 1H), 2.51(t, 2H), 2.08(m, 1H), 1.76(m,6H), 1.54(m, 1H), 0.99(t, 3H) 186 (R)-2-{1-[2-(4-amino-3- ¹H-NMR(400MHz, CDCl₃) δ 8.71(s, 1H), 7.32(m, nitrophenylamino)-6- 1H), 6.76(d,1H), 6.04(s, 2H), 5.96(s, 1H), 5.00(brs,propylpyrimidin-4-yl]piperidin-2- 1H), 3.74(m, 1H), 3.55(m, 1H), 3.39(m,1H), 3.01(t, yl}ethanol 1H), 2.49(t, 2H), 2.09(m, 1H), 1.73(m, 6H),1.55(m, 1H), 0.99(t, 3H) 187 3-[4-(octahydroquinolin-1(2H)- ¹H-NMR(400MHz, CD₃OD) δ 8.26(s, 1H), 7.78(d, yl)-6-propylpyrimidin-2- 1H), 7.40(t,1H), 7.23(d, 1H), 5.99(s, 1H), 4.21(m, ylamino]benzonitrile 1H), 3.38(t,1H), 3.26(m, 1H), 2.47(m, 2H), 2.15(m, 1H), 1.86-1.58(m, 10H),1.40-1.19(m, 2H), 1.17- 1.12(m, 2H), 0.99(t, 3H) 188N-(3-nitrophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.97(s, 1H), 8.40(brs,(octahydroquinolin-1(2H)-yl)-6- NH), 7.83(d, 1H), 7.64(d, 1H), 7.42(t,1H), 5.83(s, propylpyrimidin-2-amine 1H), 4.45(m, 1H), 3.26(m, 2H),2.53(m, 2H), 2.11(m, 1H), 1.93-1.68(m, 8H), 1.40-1.18(m, 6H), 1.01(t,3H) 189 N-(4-fluoro-3-nitrophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.80(s,1H), 7.90(brs, (octahydroquinolin-1(2H)-yl)-6- NH), 7.55(m, 1H), 7.15(m,1H), 5.81(s, 1H), 4.39(m, propylpyrimidin-2-amine 1H), 3.21(m, 2H),2.50(m, 2H), 2.10(m, 1H), 1.78(m, 8H), 1.42-1.14(m, 6H), 1.00(t, 3H) 190N-(4-chloro-3-nitrophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.69(s, 1H),8.52(brs, (octahydroquinolin-1(2H)-yl)-6- NH), 7.47(d, 1H), 7.40(d, 1H),5.83(s, 1H), 4.37(m, propylpyrimidin-2-amine 1H), 3.23(m, 2H), 2.51(m,2H), 2.10(m, 1H), 1.79(m, 8H), 1.41-1.13(m, 6H), 1.00(t, 3H) 191N-(3-methoxyphenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.87(brs, NH), 7.30(m,(octahydroquinolin-1(2H)-yl)-6- 1H), 7.18(m, 2H), 6.59(m, 1H), 5.77(s,1H), 4.30(m, propylpyrimidin-2-amine 1H), 3.80(s, 3H), 3.33(m, 1H),3.20(m, 1H), 2.54(m, 2H), 2.15(m, 1H), 1.87-1.66(m, 8H), 1.51(m, 1H),1.38-1.28(m, 5H), 1.26(t, 3H) 192 N-(5-methoxy-2-methylphenyl)-¹H-NMR(400 MHz, CDCl₃) δ 7.71(brs, 1H), 7.06(d,4-(octahydroquinolin-1(2H)-yl)-6- 1H), 6.54(m, 1H), 5.75(s, 1H), 4.36(m,1H), 3.78(s, propylpyrimidin-2-amine 3H), 3.18(m, 2H), 2.54(t, 2H),2.30(s, 3H), 2.04(m, 1H), 1.82-1.67(m, 8H), 1.42-1.26(m, 6H), 1.01(t,3H) 193 N-(4-methoxyphenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 9.22(brs, NH),7.52(d, (octahydroquinolin-1(2H)-yl)-6- 2H), 6.86(d, 2H), 5.75(s, 1H),4.13(m, 1H), 3.80(s, propylpyrimidin-2-amine 3H), 3.36(m, 1H), 3.20(m,1H), 2.55(t, 2H), 1.82(m, 1H), 1.84-1.66(m, 8H), 1.37-1.14(m, 6H),1.01(t, 3H) 194 4-(octahydroquinolin-1(2H)-yl)-6- ¹H-NMR(400 MHz, CDCl₃)δ 8.24(brs, NH), 8.19(s, propyl-N-(3- 1H), 7.58(d, 1H), 7.37(t, 1H),7.22(d, 1H), 5.78(s, trifluoromethylphenyl)pyrimidin- 1H), 4.38(m, 1H),3.22(m, 2H), 2.52(t, 2H), 2.10(m, 2-amine 1H), 1.86-1.66(m, 8H),1.45-1.12(m, 6H), 1.00(t, 3H)

TABLE 1-21 Example Compound NMR Spectrum 195 N-(3-chlorophenyl)-4-¹H-NMR(400 MHz, CDCl₃) δ 8.33(brs, NH), 7.86(s,(octahydroquinolin-1(2H)-yl)-6- 1H), 7.36(d, 1H), 7.82(t, 1H), 6.97(d,1H), 5.80(s, propylpyrimidin-2-amine 1H), 4.20(m, 1H), 3.34(m, 1H),3.22(m, 1H), 2.51(t, 2H), 2.12(m, 1H), 1.86-1.63(m, 8H), 1.53-1.16(m,6H), 1.00(t, 3H) 196 N-(5-chloro-2-methylphenyl)-4- ¹H-NMR(400 MHz,CDCl₃) δ 8.29(s, 1H), 7.07(d, (octahydroquinolin-1(2H)-yl)-6- 1H),6.90(d, 1H), 5.78(s, 1H), 4.29(m, 1H), 3.21(m, propylpyrimidin-2-amine2H), 2.50(m, 2H), 2.31(s, 3H), 2.04(m, 1H), 1.89- 1.64(m, 8H),1.51-1.12(m, 6H), 1.02(t, 3H) 197 N-(3-chloro-4-methylphenyl)-4-¹H-NMR(400 MHz, CDCl₃) δ 8.90(brs, NH), 7.81(s,(octahydroquinolin-1(2H)-yl)-6- 1H), 7.31(d, 1H), 7.13(d, 1H), 5.79(s,1H), 4.20(m, propylpyrimidin-2-amine 1H), 3.35(m, 1H), 3.24(m, 1H),2.54(m, 2H), 2.32(s, 3H), 2.11(m, 1H), 1.87-1.64(m, 8H), 1.55-1.14(m,6H), 1.01(t, 3H) 198 N-(3-methylthiophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ8.38(brs, NH), 7.59(s, (octahydroquinolin-1(2H)-yl)-6- 1H), 7.39(d, 1H),7.20(m, 1H), 6.89(d, 1H), 5.77(s, propylpyrimidin-2-amine 1H), 4.29(m,1H), 3.32-3.21(m, 2H), 2.48(m, 2H + 3H), 2.14(m, 1H), 1.86-1.65(m, 8H),1.49- 1.15(m, 6H), 1.00(t, 3H) 199 N-[4-(octahydroquinolin-1(2H)-¹H-NMR(400 MHz, CDCl₃) δ 9.03(brs, NH), 8.37(s,yl)-6-propylpyrimidin-2-yl]-1H- NH), 7.92(s, 1H), 7.31(m, 2H), 7.19(s,1H), 6.47(s, indol-5-amine 1H), 5.74(s, 1H), 4.13(m, 1H), 3.39-3.21(m,2H), 2.56(m, 2H), 2.19(m, 1H), 1.85-1.62(m, 8H), 1.68- 1.25(m, 6H),1.01(t, 3H) 200 N-[4-(octahydroquinolin-1(2H)- ¹H-NMR(400 MHz, CDCl₃) δ9.12(brs, NH), 7.98(s, yl)-6-propylpyrimidin-2-yl]-2- 1H), 7.63(d, 1H),7.40(d, 1H), 5.76(s, 1H), 4.24(m, (trifluoromethyl)-1H- 1H),3.26-3.13(m, 2H), 2.53(m, 2H), 2.05(m, 1H), benzo[d]imidazol-5-amine1.83-1.62(m, 8H), 1.35-1.10(m, 6H), 0.99(t, 3H) 201N-[4-(octahydroquinolin-1(2H)- ¹H-NMR(400 MHz, CDCl₃) δ 8.76(s, 1H),8.16(s, yl)-6-propylpyrimidin-2- 1H), 8.04-7.93(m, 3H), 7.35(m, 1H),5.81(s, 1H), yl]quinolin-6-amine 4.28(m, 1H), 3.35-3.25(m, 2H), 2.54(m,2H), 2.27(m, 1H), 1.79-1.75(m, 8H), 1.25(m, 6H), 1.02(m, 3H) 2024-methyl-7-[4- ¹H-NMR(400 MHz, CD₃OD) δ 8.11(s, 1H), 7.61(d,(octahydroquinolin-1(2H)-yl)-6- 1H), 7.44(d, 1H), 6.13(s, 1H), 6.01(s,1H), 4.37(m, propylpyrimidin-2-amino]-2H- 1H), 3.40(m, 1H), 3.24(m, 1H),2.51(t, 2H), 2.47(s, chromen-2-one 3H), 2.16(m, 1H), 1.86-1.67(m, 8H),1.44-1.15(m, 6H), 1.13(t, 3H) 203 N-[4-(octahydroquinolin-1(2H)-¹H-NMR(400 MHz, CDCl₃) δ 8.99(s, 1H), 8.61(s, yl)-6-propylpyrimidin-2-1H), 8.03(m, 1H), 7.73(m, 1H), 7.56-7.49(m, 2H), yl]quinolin-3-amine5.83(s, 1H), 4.40(m, 1H), 3.25(m, 2H), 2.51(m, 2H), 2.13(m, 1H),1.87-1.35(m, 8H), 1.26-1.02(m, 6H), 0.84(m, 3H) 204N-[4-(octahydroquinolin-1(2H)- ¹H-NMR(400 MHz, CD₃OD) δ 7.56(d, 1H),7.48(s, yl)-6-propylpyrimidin-2-yl]-1H- 1H), 7.26(s, 1H), 7.06(m, 1H),6.45(s, 1H), 6.26(s, indol-6-amine hydrochloride 1H), 4.40-4.10(brs,1H), 3.40(m, 2H), 2.58(m, 2H), 2.04(m, 1H), 1.82-1.72(m, 8H),1.34-1.23(m, 6H), 1.03(m, 3H)

TABLE 1-22 Example Compound NMR Spectrum 205 (R)-5-{4-[3- ¹H-NMR(400MHz, CDCl₃) δ 8.15(s, 1H), 7.60(br, (ethylamino)piperidin-1-yl]-6- 1H),7.48(d, 1H), 7.18(d, 1H), 5.95(s, 1H), 4.34(m,propylpyrimidin-2-ylamino}-2- 1H), 4.05(m, 1H), 3.12(m, 1H), 2.93(m,1H), 2.88(m, methylbenzonitrile 2H), 2.48(m, 5H), 2.06(m, 3H), 1.82(m,1H), 1.77(m, 2H), 1.56(m, 1H), 1.43(m, 1H), 1.15(t, 3H), 0.98(t, 3H) 206(R)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.12(s, 1H), 7.59(d,(propylamino)piperidin-1-yl]-6- 1H), 7.21(d, 1H), 5.97(s, 1H), 4.47(m,1H), 4.13(br, propylpyrimidin-2-ylamino}-2- 1H), 3.27(m, 1H), 3.17(m,1H), 2.92(m, 1H), 2.77(m, methylbenzonitrile 2H), 2.51(m, 2H), 2.49(s,3H), 2.16(m, 1H), 1.94(m, 1H), 1.76-1.57(m, 5H), 1.26(m, 2H), 1.01(t,3H), 0.92(t, 3H) 207 (R)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.11(s, 1H),7.55(d, (butylamino)piperidin-1-yl]-6- 1H), 7.49(br, 1H), 7.20(d, 1H),5.96(s, 1H), 4.40(m, propylpyrimidin-2-ylamino}-2- 1H), 4.05(m, 1H),3.08(m, 1H), 3.00(m, 1H), 2.74(m, methylbenzonitrile 3H), 2.51(m, 5H),2.09(m, 1H), 1.85(m, 1H), 1.74(m, 2H), 1.56(m, 4H), 1.35(m, 2H), 1.00(t,3H), 0.92(t, 3H) 208 (R)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.11(s, 1H), 7.53(dd, (pentylamino)piperidin-1-yl]-6- 1H), 7.48(br, 1H),7.18(d, 1H), 5.96(s, 1H), 4.37(m, propylpyrimidin-2- 1H), 4.05(m, 1H),3.10(m, 1H), 3.01(m, 1H), 2.73(m, ylamino}benzonitrile 3H), 2.49(m, 5H),2.09(m, 1H), 1.83(m, 1H), 1.74(m, 3H), 1.55(m, 2H), 1.53(m, 3H), 1.30(m,4H), 0.98(t, 3H), 0.87(t, 3H) 209 (R)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.09(s, 1H), 7.53(d, (isobutylamino)piperidin-1-yl]-6- 1H), 7.50(br,1H), 7.18(d, 1H), 5.95(s, 1H), 4.28(m, propylpyrimidin-2-ylamino}-2-1H), 4.05(m, 1H), 3.10(m, 1H), 2.94(m, 1H), 2.63(m, methylbenzonitrile1H), 2.59-2.44(m, 7H), 2.05(m, 2H), 1.83(m, 1H), 1.72(m, 3H), 1.58(m,1H), 1.46(m, 1H), 1.00(t, 3H), 0.90(m, 6H) 210 (R)-5-{4-[3- ¹H-NMR(400MHz, CDCl₃) δ 8.55(br, 1H), 8.09(s, (isopentylamino)piperidin-1-yl]-6-1H), 7.58(d, 1H), 7.20(d, 1H), 6.00(s, 1H), 4.60(m,propylpyrimidin-2-ylamino}-2- 1H), 4.01(m, 1H), 3.22(m, 1H), 3.07(m,1H), 2.92(m, methylbenzonitrile 1H), 2.87(m, 2H), 2.52(m, 2H), 2.48(s,3H), 2.24(m, 1H), 1.89(m, 1H), 1.62(m, 1H), 1.59(m, 3H), 1.55(m, 4H),0.98(t, 3H), 0.85(m, 6H) 211 (R)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz,CDCl₃) δ 8.07(s, 1H), 7.56(d, (neopentylamino)piperidin-1-yl]- 1H),7.19(d, 1H), 7.13(br, 1H), 5.95(s, 1H), 4.26(m, 6-propylpyrimidin-2-1H), 4.06(m, 1H), 3.11(m, 1H), 2.91(m, 1H), 2.56(m, ylamino}benzonitrile1H), 2.47(m, 5H), 2.02(m, 1H), 1.83(m, 1H), 1.79(m, 2H), 1.69(m, 3H),1.57(m, 2H), 1.00(t, 3H), 0.90(s, 9H) 212 (R)-5-{4-[3- ¹H-NMR(400 MHz,CDCl₃) δ 8.11(s, 1H), 7.55(d, (isopropylamino)piperidin-1-yl]- 1H),7.20(d, 1H), 5.96(s, 1H), 4.57(m, 1H), 4.09(m,6-propylpyrimidin-2-ylamino}-2- 1H), 3.27-3.14(m, 3H), 2.98(m, 1H),2.53-2.49(s, methylbenzonitrile 5H), 2.16(m, 1H), 1.88(m, 1H), 1.71(m,3H), 1.60(m, 2H), 1.24(m, 6H), 0.99(t, 3H)

TABLE 1-23 Example Compound NMR Spectrum 213 (R)-5-(4-{3-[(1H-pyrrol-2-¹H-NMR(400 MHz, CDCl₃) δ 9.12(br, 1H), 8.32(s,yl)methylamino]piperidin-1-yl}-6- 1H), 7.46(d, 1H), 7.20(d, 1H), 6.75(s,1H), 6.11(s, propylpyrimidin-2-ylamino)-2- 1H), 6.02(s, 1H), 5.86(s,1H), 4.32(br, 1H), 3.92(m, methylbenzonitrile 3H), 3.08 (m, 1H), 2.96(m,1H), 2.75(m, 1H), 2.52- 2.48(m, 5H), 2.05(m, 1H), 1.83(m, 1H), 1.72(m,3H), 1.58(m, 1H), 1.46(m, 1H), 0.97(m, 3H) 214(R)-2-methyl-5-(4-propyl-6-{3- ¹H-NMR(400 MHz, CDCl₃) δ 8.12(s, 1H),7.51(dd, [(thiophen-2- 1H), 7.20-7.16(m, 2H), 7.11(br, 1H), 6.94-6.91(m,ylmethyl)amino]piperidin-1- 2H), 5.92(s, 1H), 4.25(m, 1H), 4.07(m, 2H),4.04(m, yl}pyrimidin-2- 1H), 3.08(m, 1H), 2.99(m, 1H), 2.72(m, 1H),2.46(m, ylamino)benzonitrile 5H), 1.99(m, 1H), 1.80(m, 1H), 1.71(m, 2H),1.58- 1.45(m, 3H), 0.98(t, 3H) 215 (R)-5-(4-{3-[(4,5-dimethylfuran-¹H-NMR(400 MHz, CDCl₃) δ 8.10(s, 1H), 7.55(m,2-ylmethyl)amino]piperidin-1-yl}- 1H), 7.44(br, 1H), 7.18(d, 1H),5.92(s, 1H), 4.13- 6-propylpyrimidin-2-ylamino)-2- 4.09(m, 2H), 3.76(s,2H), 3.02(m, 1H), 2.90(m, 1H), methylbenzonitrile 2.66(m, 5H), 2.49(s,3H), 2.01(m, 1H), 1.89(s, 3H), 1.77(m, 1H), 1.69(m, 3H), 1.55(m, 1H),1.47(m, 1H), 0.98(t, 3H) 216 (R)-2-methyl-5-{4-[3-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.15(s, 1H), 7.58(br, methylthiopropylamino)piperidin- 1H),7.49(d, 1H), 7.18(d, 1H), 5.96(s, 1H), 4.30(m,1-yl]-6-propylpyrimidin-2- 1H), 4.05(m, 1H), 3.09(m, 1H), 2.81(m, 1H),2.78(m, ylamino}benzonitrile 2H), 2.67(m, 1H), 2.55(t, 2H), 2.47(m, 5H),2.09(s, 3H), 2.01(m, 1H), 1.79(m, 2H), 1.69(m, 3H), 1.61(m, 1H), 1.41(m,1H), 0.98(t, 3H) 217 (R)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.10(d, 1H),7.53(dd, (cyclopropylmethylamino)piperidin- 1H), 7.30(br, 1H), 7.18(d,1H), 5.96(s, 1H), 4.30(m, 1-yl]-6-propylpyrimidin-2- 1H), 4.01(m, 1H),3.09(m, 1H), 2.96(m, 1H), 2.72(m, ylamino}-2-methylbenzonitrile 1H),2.59(m, 1H), 2.52(m, 1H), 2.49(m, 5H), 2.01(m, 2H), 1.82(m, 1H), 1.75(m,2H), 1.59(m, 1H), 1.48(m, 1H), 0.98(t, 3H), 0.49(m, 2H), 0.15(m, 2H) 218(R)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.08(s, 1H), 7.57(d,(cyclopentylmethylamino)piperidin- 1H), 7.47(br, 1H), 7.18(d, 1H),5.96(s, 1H), 4.36(m, 1-yl]-6-propylpyrimidin-2- 1H), 4.06(m, 1H),3.07(m, 1H), 2.96(m, 1H), 2.72- ylamino}-2-methylbenzonitrile 2.62(m,3H), 2.51-2.48(s, 5H), 2.07(m, 2H), 1.81(m, 4H), 1.57(m, 6H), 1.18(m,2H), 1.00(t, 3H) 219 (R)-5-{4-[3-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.04(s,1H), 7.68(br, hydroxybenzylamino)piperidin-1- 1H), 7.49(d, 1H), 7.16(d,1H), 7.09(d, 2H), 6.70(d, yl]-6-propylpyrimidin-2-ylamino}- 2H), 5.90(s,1H), 4.24(br, 1H), 3.95(br, 1H), 3.75(m, 2-methylbenzonitrile 2H),3.16(m, 1H), 3.07(m, 1H), 2.71(m, 1H), 2.49(m, 2H), 2.44(s, 3H), 1.99(m,1H), 1.79(m, 1H), 1.74(m, 2H), 1.50(m, 3H), 0.99(t, 3H) 220(R)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.92(m, 1H), 7.64(m,methylphenylamino)-6- 1H), 7.44(m, 1H), 6.54-6.43(m, 1H), 4.63-4.22(m,propylpyrimidin-4-yl]piperidin-3- 1H), 4.01(m, 1H), 3.85(m, 1H),3.54-3.13(m, 1H), yl}acetamide hydrochloride 3.43(m, 1H), 2.64(m, 2H),2.52(s, 3H), 2.01(m, 1H), 1.99(d, 4H), 1.77(m, 2H), 1.66(m, 2H), 1.05(t,3H) 221 (R)-3-[4-(3-aminopiperidin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ7.96(s, 1H), 7.80(m, 6-propylpyrimidin-2- 1H), 7.62-7.59(m, 2H), 6.60(s,1H), 4.09(m, 1H), ylamino]benzonitrile 3.59-3.42(m, 3H), 2.69(m, 2H),2.20(m, 1H), dihydrochloride 1.95(m, 1H), 1.82-1.77(m, 4H), 1.25(m, 1H),1.04(t, 3H)

TABLE 1-24 Example Compound NMR Spectrum 222(R)-5-[4-(3-aminopiperidin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ 7.95(s, 1H),7.83(m, 6-propylpyrimidin-2-ylamino]-2- 1H), 7.45(m, 1H), 6.59(s, 1H),4.45(brs, 1H), fluorobenzonitrile 4.11(brs, 1H), 3.55-3.40(m, 3H),2.67(m, 2H), dihydrochloride 2.19(m, 1H), 1.96(m, 1H), 1.81-1.76(m, 4H),1.06(t, 3H) 223 (R)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.20(s, 1H),7.64(m, (propylamino)piperidin-1-yl]-6- 1H), 7.33(m, 1H), 7.21(m, 2H),5.99(s, 1H), 4.33(m, propylpyrimidin-2- 1H), 4.05(m, 1H), 3.07(t, 1H),2.88(t, 1H), 2.67(m, ylamino}benzonitrile 3H), 2.48(m, 2H), 1.73(m, 3H),1.53-1.41(m, 4H), 1.26(m, 1H), 0.98(m, 3H), 0.92(m, 3H) 224 (R)-3-{4-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.97(s, 1H), 7.78(m,(cyclopropylmethylamino)piperidin- 1H), 7.61(m, 2H), 6.64(s, 1H),4.57(m, 1H), 1-yl]-6-propylpyrimidin-2- 4.50(brs, 1H), 3.61-3.40(m, 3H),2.86(m, 2H), ylamino}benzonitrile 2.68(t, 2H), 2.28(m, 1H), 1.97(m, 1H),1.87-1.73(m, dihydrochloride 4H), 1.06(t, 4H), 0.69(m, 2H), 0.35(m, 2H)225 (R)-2-fluoro-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.14(s, 1H), 7.61(m,(propylamino)piperidin-1-yl]-6- 1H), 7.23(brs, 1H), 7.09(m, 1H), 5.98(s,1H), propylpyrimidin-2- 4.30(m, 1H), 4.10(m, 1H), 3.09(t, 1H), 2.89(t,1H), ylamino}benzonitrile 2.67(m, 3H), 2.46(m, 2H), 1.80-1.69(m, 3H),1.55- 1.26(m, 4H), 1.26(m, 1H), 1.00-0.91(m, 6H) 226 (R)-5-{4-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.97(s, 1H), 7.82(m,(cyclopropylmethylamino)piperidin- 1H), 7.46(m, 1H), 6.61(s, 1H),4.55(m, 1H), 4.20- 1-yl]-6-propylpyrimidin-2- 4.04(brs, 1H), 3.55(m,2H), 3.38(m, 1H), 2.87(m, ylamino}-2-fluorobenzonitrile 2H), 2.67(t,2H), 2.26(m, 1H), 1.96(m, 1H), 1.79(m, dihydrochloride 2H), 1.72(m, 2H),1.06(t, 4H), 0.71(m, 2H), 0.37(m, 2H) 227 (R)-N¹-{4-[3- ¹H-NMR(400 MHz,CDCl₃) δ 7.11(d, 1H), 6.88- (cyclopropylmethylamino)piperidin- 6.84(m,2H), 5.92(s, 1H), 4.55(m, 1H), 3.95-3.89(m,1-yl]-6-propylpyrimidin-2-yl}-4- 3H), 3.14(t, 2H), 2.90(m, 1H), 2.67(m,2H), 2.51(t, fluorobenzene-1,3-diamine 2H), 2.12(m, 1H), 1.89(m, 1H),1.78-1.55(m, 4H), 1.00-1.97(m, 4H), 0.53(m, 2H), 0.21(m, 2H) 228(R)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.81(s, 1H), 7.97(brs,(cyclopropylmethylamino)piperidin- 1H), 7.34(d, 1H), 6.77(d, 1H),5.97(s, 2H), 4.40(m, 1-yl]-6-propylpyrimidin-2-yl}-3- 1H), 4.11(m, 1H),3.16(m, 2H), 2.82(m, 1H), 2.58- nitrobenzene-1,4-diamine 2.50(m, 4H),2.10(m, 1H), 1.88(m, 1H), 1.76(m, 2H), 1.59(m, 2H), 0.99(m, 4H), 0.50(m,2H), 0.14(m, 2H) 229 (R)-3-amino-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ7.66(brs, 1H), 7.36(s, (cyclopropylmethylamino)piperidin- 1H), 7.20(s,1H), 6.53(s, 1H), 5.98(s, 1H), 4.45(m, 1-yl]-6-propylpyrimidin-2- 1H),4.00(m, 3H), 3.12(m, 2H), 2.91(m, 1H), 2.68(m, ylamino}benzonitrile 2H),2.49(m, 2H), 2.11(m, 2H), 1.83(m, 1H), 1.74- 1.48(m, 4H), 0.98(m, 4H),0.52(m, 2H), 0.21(m, 2H) 230 (R)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ7.82(s, 1H), 7.67(brs, (cyclopropylmethylamino)piperidin- 1H), 7.15(d,1H), 6.58(d, 1H), 5.79(s, 1H), 4.17(m, 1-yl]-6-propylpyrimidin-2-yl}-3-1H), 3.89(m, 3H), 2.98-2.91(m, 2H), 2.63(m, 1H),(trifluoromethyl)benzene-1,4- 2.42-2.37(m, 4H), 1.95(m, 1H),1.69-1.62(m, 3H), diamine 1.42(m, 2H), 0.86(m, 4H), 0.36(m, 2H), 0.00(m,2H) 231 (R)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.08(brs, 1H), 7.45(s,(cyclopropylmethylamino)piperidin- 1H), 7.00(s, 1H), 6.54(s, 1H),5.98(s, 1H), 4.02(m, 1-yl]-6-propylpyrimidin-2-yl}-5- 1H), 4.00(m, 3H),3.24-3.13(m, 2H), 2.93(m, 1H), (trifluoromethyl)benzene-1,3- 2.67(m,2H), 2.50(m, 2H), 2.14(m, 1H), 1.89(m, 1H), diamine 1.60(m, 4H), 0.98(m,4H), 0.53(m, 2H), 0.20(m, 2H)

TABLE 1-25 Example Compound NMR Spectrum 232 (R)-N-{1-[2-(4-amino-3-¹H-NMR(400 MHz, CD₃OD) δ 8.41(s, 1H), 7.41(d, nitrophenylamino)-6- 1H),6.99(d, 1H), 6.51(s, 1H), 4.09(brs, 2H), 3.83(m,butylpyrimidin-4-yl]piperidin-3- 1H), 3.30(m, 2H), 2.63(t, 2H), 2.01(m,1H), 1.94(s, yl}acetamide hydrochloride 3H + 1H), 1.68(m, 4H), 1.44(m,2H), 1.00(t, 3H) 233 (R)-N-{1-[6-butyl-2-(4-methyl-3- ¹H-NMR(400 MHz,CD₃OD) δ 8.51(s, 1H), 7.57(d, nitrophenylamino)pyrimidin-4- 1H), 7.46(d,1H), 6.53(m, 1H), 4.75-4.06(m, 2H), yl]piperidin-3-yl}acetamide 3.84(m,1H), 3.59-3.13(m, 2H), 2.69(t, 2H), 2.55(s, hydrochloride 3H), 2.10(m,1H), 1.95(s, 3H + 1H), 1.71(m, 4H), 1.45(m, 2H), 1.00(t, 3H) 234(R)-N-{1-[6-butyl-2-(4-fluoro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.60(s, 1H),7.74(m, nitrophenylamino)pyrimidin-4- 1H), 7.46(t, 1H), 6.53(s, 1H),4.78-3.97(m, 2H), yl]piperidin-3-yl}acetamide 3.81(m, 1H), 3.50-3.08(m,2H), 2.68(m, 2H), hydrochloride 2.03(m, 1H), 1.93(s, 3H + 1H), 1.69(m,4H), 1.47(m, 2H), 1.00(t, 3H) 235 (R)-N-{1-[6-butyl-2-(4-chloro-3-¹H-NMR(400 MHz, CD₃OD) δ 8.46(s, 1H), 7.66(s,nitrophenylamino)pyrimidin-4- 2H), 6.56(s, 1H), 4.80-4.12(m, 2H),3.82(m, 1H), yl]piperidin-3-yl}acetamide 3.50-3.07(m, 2H), 2.68(t, 2H),2.02(m, 1H), 1.95(s, hydrochloride 3H + 1H), 1.70(m, 4H), 1.44(m, 2H),1.00(t, 3H) 236 (R)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ7.21-6.97(m, 2H), cyanophenylamino)-6- 6.73(s, 1H), 6.48(s, 1H), 4.10(m,2H), 3.85(m, 1H), butylpyrimidin-4-yl]piperidin-3- 3.50-3.13(m, 2H),2.65(t, 2H), 2.04(m, 1H), 1.96(s, yl}acetamide hydrochloride 3H + 1H),1.69(m, 4H), 1.44(m, 2H), 1.00(t, 3H) 237 (R)-N-{1-[2-(3-amino-5-¹H-NMR(400 MHz, CD₃OD) δ 7.20-6.93(m, 2H),trifluoromethylphenylamino)-6- 6.73(s, 1H), 6.46(s, 1H), 4.73-4.07(m,2H), 3.86(m, butylpyrimidin-4-yl]piperidin-3- 1H), 3.13(m, 2H), 2.65(t,2H), 2.03(m, 1H), 1.95(s, yl}acetamide hydrochloride 3H + 1H), 1.69(m,4H), 1.44(m, 2H), 0.98(t, 3H) 238 (R)-N-{1-[2-(4-amino-3- ¹H-NMR(400MHz, CD₃OD) δ 7.58(s, 1H), 7.31(m, trifluoromethylphenylamino)-6- 1H),6.86(d, 1H), 6.37(s, 1H), 4.48-4.11(m, 2H),butylpyrimidin-4-yl]piperidin-3- 3.82(m, 1H), 3.50(m, 2H), 2.62(t, 2H),2.01-1.89(m, yl}acetamide hydrochloride 1H + 3H + 1H), 1.67(m, 4H),1.43(m, 2H), 0.99(t, 3H) 239 (R)-N-{1-[6-butyl-2-(4-fluoro-3- ¹H-NMR(400MHz, CD₃OD) δ 8.06-7.70(m, 2H), trifluoromethylphenylamino)pyrim-7.38(t, 1H), 6.54-6.44(m, 1H), 4.57-4.02(m, 2H), idin-4-yl]piperidin-3-3.83(m, 1H), 3.48-3.13(m, 2H), 2.67(t, 2H), 2.01(m, yl}acetamidehydrochloride 1H), 1.94(s, 1H + 3H), 1.74-1.65(m, 4H), 1.45(m, 2H),1.00(t, 3H) 240 (R)-N-{1-[6-butyl-2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ7.98(s, 1H), 7.82(s, fluorophenylamino)pyrimidin-4- 1H), 7.41(t, 1H),6.52(brs, 1H), 4.63-4.07(m, 2H), yl]piperidin-3-yl}acetamide 3.82(m,1H), 3.50-3.10(m, 2H), 2.67(t, 2H), 2.01(m, hydrochloride 1H), 1.96(s,1H + 3H), 1.68(m, 4H), 1.47(m, 2H), 1.00(t, 3H) 241(R)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.15(brs, 1H), 6.95(t,fluorophenylamino)-6- 1H), 6.65(m, 1H), 6.41(m, 1H), 4.70-3.85(m, 3H),butylpyrimidin-4-yl]piperidin-3- 3.56-3.20(m, 2H), 2.62(t, 2H), 2.02(m,1H), 1.96(s, yl}acetamide hydrochloride 1H + 3H), 1.68(m, 4H), 1.45(m,2H), 0.99(t, 3H)

TABLE 1-26 Example Compound NMR Spectrum 242 (R)-N-{1-[2-(3-amino-4-¹H-NMR(400 MHz, CD₃OD) δ 7.18-7.16(m, 2H), chlorophenylamino)-6- 6.68(m,1H), 6.43(s, 1H), 4.71-3.86(m, 3H), 3.50-butylpyrimidin-4-yl]piperidin-3- 3.10(m, 2H), 2.63(t, 2H), 2.02(m, 1H),1.97(s, yl}acetamide hydrochloride 1H + 3H), 1.70(m, 4H), 1.43(m, 2H),0.99(t, 3H) 243 (R)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 7.48(s,1H), 7.35(m, cyanophenylamino)-6- 1H), 6.84(d, 1H), 6.39(brs, 1H),4.56-4.02(m, 2H), butylpyrimidin-4-yl]piperidin-3- 3.82(m, 1H),3.50-3.13(m, 2H), 2.62(t, 2H), 2.01- yl}acetamide hydrochloride 1.89(m,1H + 3H + 1H), 1.66(m, 4H), 1.43(m, 2H), 0.99(t, 3H) 244(R)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.47(s, NH), 7.20-methylphenylamino)-6- 7.15(m, 2H), 6.80(m, 1H), 5.98(s, 1H), 4.45(m,1H), propylpyrimidin-4-yl]piperidin-3- 4.17(m, 1H), 4.02(d, 2H), 3.85(m,1H), 3.17(m, 1H), yl}-2-hydroxyacetamide 3.07(m, 1H), 2.45(m, 5H),2.13(m, 1H), 1.81(m, 1H), 1.71(m, 2H), 1.55(m, 2H), 0.97(t, 3H) 245(R)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.60(brs, NH), 7.36-cyanophenylamino)-6- 7.31(m, 2H), 7.22-7.16(m, 2H), 6.75(m, 1H), 6.01(s,propylpyrimidin-4-yl]piperidin-3- 1H), 4.50(m, 1H), 4.14(m, 1H), 4.02(d,2H), 3.84(m, yl}-2-hydroxyacetamide 1H), 3.15(m, 1H), 3.07(m, 1H),2.48(m, 5H), 2.16(m, 1H), 1.81(m, 1H), 1.73(m, 2H), 1.56(m, 2H), 0.98(t,3H) 246 (R)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.99(s, 1H),7.83(m, fluorophenylamino)-6- 1H), 7.37(m, 1H), 6.46(s, 1H), 4.42(m,1H), 4.15- propylpyrimidin-4-yl]piperidin-3- 3.90(m, 4H), 3.34(m, 1H),3.15(m, 1H), 2.61(m, 2H), yl}-2-hydroxyacetamide 2.00(m, 1H), 1.88(m,1H), 1.75(m, 3H), 1.63(m, 1H), 1.04(t, 3H) 247 (R)-N-(1-{2-[3-amino-5-¹H-NMR(400 MHz, CDCl₃) δ 7.26(s, 1H), 6.68(m,(trifluoromethyl)phenylamino]-6- 1H), 6.49(m, 1H), 5.94(s, 1H), 4.17(m,1H), 4.06(s, propylpyrimidin-4-yl}piperidin-3- 2H), 3.65(m, 1H), 3.42(m,2H), 2.45(m, 2H), 2.00(m, yl)-2-hydroxyacetamide 1H), 1.79(m, 1H),1.70(m, 4H), 0.97(t, 3H) 248 (R)-N-(1-{2-[4-amino-3- ¹H-NMR(400 MHz,CDCl₃) δ 8.01(s, 1H), 6.72(m, (trifluoromethyl)phenylamino]-6- 1H),6.63(m, 1H), 5.94(s, 1H), 4.04(m, 3H), 3.86-propylpyrimidin-4-yl}piperidin-3- 3.58(m, 4H), 2.47(m, 2H), 2.02(m, 1H),1.75- yl)-2-hydroxyacetamide 1.67(m, 5H), 0.98(t, 3H) 249(R)-N-(1-{2-[4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.26(s, NH), 7.45(m,(trifluoromethyl)phenylamino]-6- 1H), 7.11(t, 1H), 6.55(m, 1H), 6.01(s,1H), 4.09(m, propylpyrimidin-4-yl}piperidin-3- 3H), 3.99(m, 1H), 3.78(m,1H), 3.42(m, 2H), 2.49(m, yl)-2-hydroxyacetamide 2H), 2.01(m, 1H),1.76-1.62(m, 5H), 0.98(t, 3H) 250 (R)-N-{1-[2-(3-amino-4- ¹H-NMR(400MHz, CDCl₃) δ 7.48(m, NH), 6.86(t, fluorophenylamino)-6- 1H), 6.71(m,1H), 6.48(m, 1H), 5.89(s, 1H), 4.24- propylpyrimidin-4-yl]piperidin-3-4.15(m, 2H), 4.08(s, 2H), 3.60(m, 1H), 3.40(m, 2H),yl}-2-hydroxyacetamide 2.45(m, 2H), 2.00(m, 1H), 1.80-1.67(m, 5H),0.97(t, 3H) 251 (R)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.52(s,NH), 7.07(d, chlorophenylamino)-6- 1H), 6.70(m, 1H), 6.47(m, 1H),5.89(s, 1H), 4.53(s, propylpyrimidin-4-yl]piperidin-3- 2NH), 4.30(m,1H), 4.09(m, 3H), 3.61(m, 1H), yl}-2-hydroxyacetamide 3.32(m, 2H),2.46(m, 2H), 2.01(m, 1H), 1.80- 1.68(m, 5H), 0.97(t, 3H)

TABLE 1-27 Example Compound NMR Spectrum 252 (R)-N-{1-[2-(3-amino-4-¹H-NMR(400 MHz, CDCl₃) δ 7.38(s, NH), 7.07(s, methylphenylamino)-6- NH),6.90(m, 1H), 6.80(d, 1H), 6.54(m, 1H), 5.80(s,propylpyrimidin-4-yl]piperidin-3- 1H), 4.26(m, 1H), 4.04(m, 3H), 3.56(m,1H), 3.26(m, yl}-2-hydroxyacetamide 1H), 3.15(m, 1H), 2.41(m, 2H),2.09(s, 3H), 1.88(m, 1H), 1.67(m, 2H), 1.59-1.46(m, 3H), 0.96(t, 3H) 253(R)-N-{1-[2-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.81(s, NH), 7.19(m,methylphenylamino)-6- 1H), 7.10(m, 1H), 6.67(m, 1H), 5.96(s, 1H),4.26(m, propylpyrimidin-4-yl]piperidin-3- 1H), 4.09(m, 3H), 3.82(m, 1H),3.65-3.61(m, 3H), yl}-2-hydroxyacetamide 2.47(m, 2H), 2.31(s, 3H),1.96(m, 1H), 1.75-1.69(m, 5H), 0.98(t, 3H) 254(R)-2-hydroxy-N-(1-{2-[4-methyl- ¹H-NMR(400 MHz, CDCl₃) δ 8.26(s, NH),7.34(d, 3-(trifluoromethyl)phenylamino]- 1H), 7.17(m, 1H), 7.00(brs,NH), 6.63(m, 1H), 6-propylpyrimidin-4-yl}piperidin- 5.98(s, 1H), 4.04(m,3H), 3.85(m, 1H), 3.70(m, 1H), 3-yl)acetamide 3.52(m, 2H), 2.48(m, 2H),2.41(s, 3H), 1.96(m, 1H), 1.74-1.69(m, 5H), 0.97(t, 3H) 255(R)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz, CDCl₃) δ 7.33(s, NH), 7.14(s,cyanophenylamino)-6- 1H), 7.13(brs, NH), 6.78(m, 1H), 6.46(s, 1H),propylpyrimidin-4-yl]piperidin-3- 5.95(s, 1H), 4.52(m, 1H), 4.23-4.03(m,5H), 3.76(m, yl}-2-hydroxyacetamide 1H), 3.15(m, 2H), 2.47(m, 2H),2.17(m, 1H), 1.81(m, hydrochloride 1H), 1.70-1.57(m, 4H), 0.97(t, 3H)256 (R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.90-7.70(m,1H), yl)-6-propylpyrimidin-2-yl]-5- 7.65-7.45(m, 1H), 7.26(s, 1H),6.62(brs, 1H), 4.50- (trifluoromethyl)benzene-1,3- 3.90(m, 2H),3.70-3.40(m, 3H), 2.69(t, 2H), 2.30- diamine dihydrochloride 2.15(m,1H), 2.05-1.90(m, 1H), 1.90-1.60(m, 4H), 1.06(t, 3H) 257(R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.70-7.25(m,2H), yl)-6-propylpyrimidin-2-yl]-3- 7.00-6.85(m, 1H), 6.48(d, 1H),4.60-3.85(m, 2H), (trifluoromethyl)benzene-1,4- 3.60-3.30(m, 3H),2.70-2.50(m, 2H), 2.20-2.10(m, diamine dihydrochloride 1H), 2.05-1.60(m,4H), 1.04(t, 3H) 258 (R)-4-(3-aminopiperidin-1-yl)-N- ¹H-NMR(400 MHz,CD₃OD) δ 7.40-7.10(m, 3H), (3-fluoro-4-methylphenyl)-6- 6.70-6.45(m,1H), 4.70-3.90(m, 2H), 3.65-3.30(m, propylpyrimidin-2-amine 3H),2.85-2.65(m, 2H), 2.27(s, 3H), 2.25-2.10(m, dihydrochloride 1H),2.05-1.90(m, 1H), 1.90-1.50(m, 4H), 1.03(t, 3H) 259(R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.33(d, 1H),7.10(t, yl)-6-propylpyrimidin-2-yl]-4- 1H), 6.87(d, 1H), 6.63(d, 1H),4.70-3.90(m, 2H), fluorobenzene-1,3-diamine 3.65-3.30(m, 3H), 2.67(t,2H), 2.25-2.15(m, 1H), dihydrochloride 2.05-1.90(m, 1H), 1.90-1.60(m,4H), 1.05(t, 3H) 260 (R)-3-amino-5-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ8.05(d, 1H), 7.82(brs, aminopiperidin-1-yl)-6- 1H), 7.46(s, 1H),6.75-6.60(m, 1H), 4.80-3.90(m, propylpyrimidin-2- 2H), 3.75-3.40(m, 3H),2.70(t, 2H), 2.30-2.15(m, yl]amino}benzonitrile 1H), 2.10-1.95(m, 1H),1.95-1.70(m, 4H), 1.06(t, dihydrochloride 3H) 261 (R)-2-amino-5-{[4-(3-¹H-NMR(400 MHz, CD₃OD) δ 7.47(d, 1H), 7.37(s, aminopiperidin-1-yl)-6-1H), 6.89(brs, 1H), 6.50(d, 1H), 4.70-3.90(m, 2H), propylpyrimidin-2-3.65-3.30(m, 3H), 2.63(t, 2H), 2.25-2.15(m, 1H), yl]amino}benzonitrile2.05-1.60(m, 5H), 1.04(t, 3H) dihydrochloride

TABLE 1-28 Example Compound NMR Spectrum 262(R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.40-7.20(m,1H), yl)-6-propylpyrimidin-2-yl]-4- 7.04(brs, 1H), 6.80(s, 1H),7.65-7.50(m, 1H), 4.75- chlorobenzene-1,3-diamine 3.90(m, 2H),3.65-3.30(m, 3H), 2.65(t, 2H), 2.25- dihydrochloride 2.15(m, 1H),2.05-1.90(m, 1H), 1.90-1.65(m, 4H), 1.05(t, 3H) 263(R)-4-(3-aminopiperidin-1-yl)-N- ¹H-NMR(400 MHz, CD₃OD) δ 7.90(d, 1H),7.59(d, [4-methyl-3- 1H), 7.44(brs, 1H), 6.57(d, 1H), 4.70-3.90(m, 2H),(trifluoromethyl)phenyl]-6- 3.70-3.30(m, 3H), 2.67(t, 2H), 2.48(s, 3H),2.25- propylpyrimidin-2-amine 2.15(m, 1H), 2.05-1.65(m, 5H), 1.06(t, 3H)dihydrochloride 264 (R)-N-[4-(3-aminopiperidin-1-yl)- ¹H-NMR(400 MHz,CD₃OD) δ 7.80-7.30(m, 4H), 6-propylpyrimidin-2-yl]-1H-indol-7.10-6.85(m, 1H), 6.54(brs, 1H), 4.70-3.90(m, 2H), 6-aminedihydrochloride 3.70-3.30(m, 3H), 2.75-2.55(m, 2H), 2.25-2.15(m, 1H),2.05-1.60(m, 5H), 1.04(t, 3H) 265 (R)-4-(3-aminopiperidin-1-yl)-N-¹H-NMR(400 MHz, CD₃OD) δ 8.52(s, 1H), 7.65- (4-methyl-3-nitrophenyl)-6-7.45(m, 2H), 6.61(brs, 1H), 4.60-3.90(m, 2H), 3.60-propylpyrimidin-2-amine 3.30(m, 3H), 2.68(t, 2H), 2.59(s, 3H),2.30-2.15(m, dihydrochloride 1H), 2.10-1.90(m, 1H), 1.90-1.60(m, 4H),1.06(t, 3H) 266 (R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ8.49(s, 1H), 7.36(d, yl)-6-propylpyrimidin-2-yl]-3- 1H), 7.04(d, 1H),6.52(brs, 1H), 4.60-3.90(m, 2H), nitrobenzene-1,4-diamine 3.60-3.30(m,3H), 2.65(t, 2H), 2.25-2.15(m, 1H), dihydrochloride 2.05-1.90(m, 1H),1.90-1.60(m, 4H), 1.05(t, 3H) 267 (R)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ7.87(s, 1H), 7.66(d, (cyclopropylmethylamino)piperidin- 1H), 7.49(d,1H), 6.62(s, 1H), 4.53(br, 1H), 4.11(br, 1-yl]-6-propylpyrimidin-2- 1H),3.63(br, 2H), 3.40(br, 1H), 2.83(br, 1H), 2.67(t,ylamino}-2-methylbenzonitrile 2H), 2.55(s, 3H), 2.01(br, 1H), 1.99(m,1H), 1.88(m, dihydrochloride 1H), 1.80(m, 2H), 1.76(m, 1H), 1.08(t, 3H),0.68(m, 2H), 0.32(m, 2H) 268 (R)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz,CD₃OD) δ 7.97(m, 1H), 7.80(m, fluorophenylamino)-6- 1H), 7.43(m, 1H),6.55-6.44(m, 1H), 4.65-4.18(m, propylpyrimidin-4-yl]piperidin-3- 1H),4.06(m, 1H), 3.82(m, 1H), 3.48-3.09(m, 1H), yl}acetamide hydrochloride3.40(m, 1H), 2.67(m, 2H), 2.01(br, 1H), 1.97(d + m, 4H), 1.77(m, 2H),1.66(m, 2H), 1.05(t, 3H) 269 (R)-5-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ8.10(s, 1H), 7.75(br, diethylaminopiperidin-1-yl)-6- 1H), 7.52(d, 1H),7.18(d, 1H), 5.96(s, 1H), 4.50- propylpyrimidin-2-ylamino]-2- 4.27(m,2H), 2.84(m, 2H), 2.70(m, 4H), 2.48(s + m, methylbenzonitrile 3 + 2H),2.04(m, 1H), 1.88(m, 1H), 1.73(m, 3H), 1.61(m, 2H), 1.10(t, 6H), 1.08(t,3H) 270 (R)-5-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.13(s, 1H), 7.90(br,diethylaminopiperidin-1-yl)-6- 1H), 7.64(m, 1H), 7.10(m, 1H), 5.97(s,1H), 4.46- propylpyrimidin-2-ylamino]-2- 4.27(m, 2H), 2.82(t, 2H),2.68(m, 4H), 2.48(t, 2H), fluorobenzonitrile dihydrochloride 2.05(m,1H), 1.88(m, 1H), 1.71(m, 2H), 1.56(m, 2H), 1.07(t, 6H), 0.98(t, 3H) 271(R)-5-[4-(3-ethylaminopiperidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.17(s, 1H),7.59(m, 1-yl)-6-propylpyrimidin-2- 1H), 7.35(br, 1H), 7.10(m, 1H),5.98(s, 1H), 4.33(br, ylamino]-2-fluorobenzonitrile 1H), 4.03(br, 1H),3.07(m, 1H), 2.90(m, 1H), 2.79- 2.70(m, 3H), 2.47(m, 2H), 2.07(m, 1H),1.81(m, 1H), 1.71(m, 2H), 1.56(m, 1H), 1.44(m, 1H), 1.16(t, 3H), 0.98(t,3H)

TABLE 1-29 Example Compound NMR Spectrum 272 (R)-N-{1-[6-butyl-2-(3-¹H-NMR(400 MHz, CD₃OD) δ 8.13(m, 1H), 8.00(s,cyanophenylamino)pyrimidin-4- 1H), 7.77(brs, 1H), 7.56(m, 2H), 6.53(brs,1H), 4.67- yl]piperidin-3-yl}acetamide 4.20(m, 1H), 4.09(m, 1H),3.85(brs, 1H), 3.48(m, hydrochloride 1H), 3.13(m, 1H), 2.67(m, 2H),1.97(m, 1H), 1.74- 1.67(s + m, 4H), 1.48(m, 4H), 1.24(m, 2H), 1.00(t,3H) 273 (R)-N-{1-[2-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.15(m, 1H), 8.01(s,cyanophenylamino)-6- 1H), 7.79(m, 1H), 7.56(m, 2H), 6.51(s, 1H),4.86(br, propylpyrimidin-4-yl]piperidin-3- 1H), 4.10(m, 1H), 3.85(brs,1H), 3.48(m, 1H), yl}acetamide hydrochloride 3.23(m, 1H), 2.65(m, 2H),2.01-1.85(m, 2H), 1.96(s, 3H), 1.80(m, 2H), 1.69(m, 2H), 1.05(t, 3H) 274(R)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ 8.20-7.22(m, 1H),cyanophenylamino)-6- 7.11(m, 1H), 6.59(s, 1H), 6.47(brs, 1H), 4.78(br,propylpyrimidin-4-yl]piperidin-3- 1H), 4.08(m, 1H), 3.85(m, 1H), 3.48(m,1H), 3.12(m, yl}acetamide hydrochloride 1H), 2.62(m, 2H), 2.04-1.85(m,2H), 1.97(s, 3H), 1.76(m, 2H), 1.68(m, 2H), 1.04(t, 3H) 275N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.41-8.22(m, 1H),nitrophenylamino)-6- 7.39(m, 1H), 6.99(m, 1H), 6.41(brs, 1H), 4.72-propylpyrimidin-4-yl]piperidin-3- 4.25(m, 1H), 4.22(m, 1H), 4.17(m, 1H),3.40(m, 1H), yl}acetamide hydrochloride 3.30(m, 1H), 2.60(m, 2H),2.01-1.90(m, 2H), 1.95(s, 3H), 1.74(m, 2H), 1.65(m, 2H), 1.04(t, 3H) 276N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.19(br, 1H), 7.98(br,fluorophenylamino)-6- 1H), 7.76(br, 1H), 7.39(m, 1H), 6.50(brs, 1H),propylpyrimidin-4-yl]piperidin-3- 4.59(m, 1H), 4.32-4.13(m, 1H),3.82(br, 1H), yl}acetamide hydrochloride 3.46(m, 1H), 3.13(m, 1H),2.63(m, 2H), 2.01- 1.90(m, 2H), 1.94(s, 3H), 1.77(m, 2H), 1.65(m, 2H),1.05(t, 3H) 277 (R)-N-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CD₃OD) δ8.22-7.18(br, 1H), trifluoromethylphenylamino)-6- 6.95(br, 1H), 6.60(br,1H), 6.43(br, 1H), 4.71- propylpyrimidin-4-yl]piperidin-3- 4.23(br, 1H),4.07(br, 1H), 3.85(br, 1H), 3.53- yl}acetamide hydrochloride 3.47(br,1H), 3.15(br, 1H), 2.59(m, 2H), 2.01(br, 2H), 1.96(s, 3H), 1.73(m, 2H),1.66(m, 2H), 1.03(t, 3H) 278 (R)-N-(1-{2-[3-ammo-5- ¹H-NMR(400 MHz,CD₃OD) δ 8.34(s, 1H), 7.71(s, (trifluoromethyl)phenylamino]-6- 1H),7.49(s, 1H), 6.62(s, 1H), 4.10(m, 1H), 3.82(m,propylpyrimidin-4-yl}piperidin-3- 1H), 3.48-3.39(m, 2H), 3.10(m, 1H),2.68(m, 2H), yl)acetamide hydrochloride 2.10-1.95(m, 2H), 2.02(s, 3H),1.79(m, 2H), 1.72(m, 2H), 1.05(m, 3H) 279 (R)-N-(1-{2-[4-amino-3-¹H-NMR(400 MHz, CD₃OD) δ 8.13-8.00(m, 1H),(trifluoromethyl)phenylamino]-6- 7.93-7.66(m, 1H), 7.53-7.41(m, 1H),6.57-6.44(m, propylpyrimidin-4-yl}piperidin-3- 1H), 4.57-4.40(m, 1H),4.09(m, 1H), 3.86(br, 1H), yl)acetamide hydrochloride 3.57-3.41(m, 1H),3.22(m, 1H), 2.66(m, 2H), 2.01- 1.94(m, 2H), 1.95(d, 3H), 1.78(m, 2H),1.67(m, 2H), 1.05(m, 3H) 280 (R)-5-[4-(3-ethylaminopiperidin- ¹H-NMR(400MHz, CD₃OD) δ 7.90(s, 1H), 7.63(m, 1-yl)-6-propylpyrimidin-2- 1H),7.48(m, 1H), 6.61(s, 1H), 4.53(br, 1H), 4.09(br,ylamino]-2-methylbenzonitrile 1H), 3.60(br, 2H), 3.43(br, 1H), 3.03(m,2H), dihydrochloride 2.66(m, 2H), 2.54(s, 3H), 2.24(m, 1H), 2.00(m, 1H),1.80(m, 4H), 1.24(m, 3H), 1.06(t, 3H)

TABLE 1-30 Example Compound NMR Spectrum 281(R)-5-[4-(3-ethylaminopiperidin- ¹H-NMR(400 MHz, CD₃OD) δ 8.00(m, 1H),7.82(m, 1-yl)-6-propylpyrimidin-2- 1H), 7.47(m, 1H), 6.64(s, 1H),4.52(br, 1H), 4.11(m, ylamino]-2-fluorobenzonitrile 1H), 3.59(m, 1H),3.48(m, 1H), 3.38(m, 1H), 3.07(m, dihydrochloride 2H), 2.68(m, 2H),2.25(m, 1H), 1.99(m, 1H), 1.79(m, 4H), 1.25(m, 3H), 1.06(t, 3H) 282(R)-2-fluoro-5-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.14-7.90(m, 1H),methylaminopiperidin-1-yl)-6- 7.72(m, 1H), 7.40(m, 1H), 6.73-6.62(m,1H), propylpyrimidin-2- 4.39(m, 1H), 3.99-3.86(m, 1H), 3.70-3.60(m, 2H),ylamino]benzonitrile 3.47(m, 1H), 2.82(m, 1H), 2.82(m, 2H), 2.60(m, 1H),dihydrochloride 2.26(br, 1H), 1.96-1.89(m, 2H), 1.81(m, 3H), 1.08(t, 3H)283 (R)-2-methyl-5-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.88(s, 1H), 7.64(d,methylaminopiperidin-1-yl)-6- 1H), 7.48(d, 1H), 6.62(s, 1H), 4.41(m,1H), 3.91(m, propylpyrimidin-2- 1H), 3.76(m, 1H), 3.60(m, 1H), 3.34(m,1H), ylamino]benzonitrile 2.77(s, 2H), 2.67(m, 3H), 2.50(s, 3H),2.24(br, 1H), dihydrochloride 1.90(m, 2H), 1.77(m, 3H), 1.04(t, 3H) 284(R)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.62-7.49(m, 2H),methylaminopiperidin-1-yl)-6- 7.22(m, 1H), 6.69-6.60(m, 1H), 4.35(m,1H), 4.10- propylpyrimidin-2-yl]-5- 4.01(m, 1H), 3.83(br, 1H), 3.39(br,1H), 2.87(m, (trifluoromethyl)benzene-1,3- 1H), 2.68(m, 2H), 2.59(m,2H), 2.24(br, 1H), 2.01- diamine dihydrochloride 1.91(m, 2H), 1.80(m,3H), 1.06(t, 3H) 285 (R)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.51-7.45(m,1H), methylaminopiperidin-1-yl)-6- 7.29-7.13(m, 1H), 7.06-6.94(m, 1H),6.62-6.53(m, propylpyrimidin-2-yl]-3- 1H), 4.32-4.20(m, 1H),3.99-3.65(m, 1H), 3.74(m, (trifluoromethyl)benzene-1,4- 1H),3.48-3.31(m, 1H), 2.80(m, 1H), 2.65(m, 2H), diamine dihydrochloride2.51(s, 2H), 2.20(m, 1H), 1.89(m, 2H), 1.77(m, 3H), 1.04(t, 3H) 286(R)-3-amino-5-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.50(m, 1H), 7.18(m,methylaminopiperidin-1-yl)-6- 1H), 6.90(m, 1H), 6.65(m, 1H),4.52-4.34(m, 1H), propylpyrimidin-2- 3.92-3.84(m, 1H), 3.62(br, 1H),3.45(m, 1H), ylamino]benzonitrile 2.81(m, 1H), 2.68(s, 4H), 2.25(br,1H), 2.00(br, 1H), dihydrochloride 1.89-1.79(m, 4H), 1.06(t, 3H) 287(R)-(4-fluoro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.00-7.65(m, 2H),trifluoromethylphenyl)-[4-(3- 7.45(m, 1H), 6.12(m, 1H), 4.29(m, 1H),4.10(m, 1H), methylaminopiperidin-1-yl)-6- 3.91(m, 1H), 3.78(m, 1H),3.45(m, 1H), 2.86- propylpyrimidin-2-yl]amine 2.77(m, 2H), 2.68(m, 2H),2.54(br, 1H), 2.23(br, dihydrochloride 1H), 1.84-1.78(m, 5H), 1.04(t,3H) 288 (R)-N¹-[4-(3-ethylaminopiperidin- ¹H-NMR(400 MHz, CD₃OD) δ8.34-8.12(m, 1H), 1-yl)-6-propylpyrimidin-2-yl]-3- 7.39(m, 1H),7.14-7.05(m, 1H), 6.48(m, 1H), nitrobenzene-1,4-diamine 4.57(m, 1H),4.12-4.09(m, 1H), 3.63(m, 1H), dihydrochloride 3.54(m, 1H), 3.21(br,1H), 2.96(m, 1H), 2.65(m, 2H), 2.25(br, 1H), 1.99(m, 1H), 1.78(m, 4H),1.24(m, 3H), 1.05(t, 3H) 289 (R)-N¹-[4-(3-ethylaminopiperidin-¹H-NMR(400 MHz, CD₃OD) δ 7.73-7.60(m, 1H),1-yl)-6-propylpyrimidin-2-yl]-4- 7.45-7.30(m, 1H), 6.91-6.86(m, 1H),6.73-6.61(m, fluorobenzene-1,3-diamine 1H), 4.52(m, 1H), 3.91-3.83(m,1H), 3.74(m, 1H), dihydrochloride 3.62(m, 2H), 3.22(m, 1H), 2.96(m, 1H),2.68(m, 2H), 2.30(br, 1H), 1.99(m, 1H), 1.81(m, 4H), 1.25(m, 3H),1.06(t, 3H)

TABLE 1-31 Example Compound NMR Spectrum 290(R)-N¹-[4-(3-ethylaminopiperidin- ¹H-NMR(400 MHz, CD₃OD) δ 7.60(m, 1H),7.39- 1-yl)-6-propylpyrimidin-2-yl]-5- 7.29(m, 1H), 7.20-6.97(m, 1H),6.78-6.55(m, 1H), (trifluoromethyl)benzene-1,3- 4.43(m, 1H),3.84-3.79(m, 1H), 3.64(m, 1H), diamine dihydrochloride 3.40(m, 1H),3.22(m, 1H), 2.83(m, 1H), 2.67(m, 2H), 2.20(m, 1H), 1.91-1.70(m, 1 +4H), 1.23(m, 3H), 1.03(t, 3H) 291 (R)-N¹-[4-(3-ethylaminopiperidin-¹H-NMR(400 MHz, CD₃OD) δ 7.90-7.63(m, 2H),1-yl)-6-propylpyrimidin-2-yl]-3- 7.36-7.29(m, 1H), 6.73-6.65(m, 1H),4.70-4.43(m, (trifluoromethyl)benzene-1,4- 1H), 4.01(m, 1H), 3.62(m,1H), 3.52(m, 1H), 3.42(m, diamine dihydrochloride 1H), 3.22-3.07(m, 1H),2.69(m, 2H), 2.26(br, 1H), 2.00(m, 1H), 1.81(m, 4H), 1.75-1.24(m, 3H),1.06(t, 3H) 292 (R)-3-amino-5-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.34(m,1H), 7.24(m, ethylaminopiperidin-1-yl)-6- 1H), 7.06(m, 1H), 6.68-6.55(m,1H), 4.51-4.38(m, propylpyrimidin-2- 1H), 3.89-3.76(m, 1H), 3.59(br,1H), 3.41(br, ylamino]benzonitrile 1H), 3.20(m, 1H), 2.98(m, 1H),2.67(m, dihydrochloride 2H), 2.24(m, 1H), 1.98(m, 1H), 1.80(m, 4H),1.23- 1.17(m, 3H), 1.05(t, 3H) 293 (R)-5-[4-(3-aminopiperidin-1-yl)-¹H-NMR(400 MHz, CD₃OD) δ 8.17(s, 1H), 7.67(d,6-butylpyrimidin-2-ylamino]-2- 1H), 7.30(d, 1H), 6.22(s, 1H), 4.25(d,1H), 3.96(m, methylbenzonitrile 1H), 3.59-3.31(m, 2H), 2.55(m, 2H),2.45(s, 3H), 2.14(m, 1H), 1.86(m, 1H), 1.75(m, 4H), 1.39(m, 2H), 0.98(t,3H) 294 (R)-5-[4-(3-aminopiperidin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ8.23(s, 1H), 7.80(m, 6-butylpyrimidin-2-ylamino]-2- 1H), 7.26(m, 1H),6.23(s, 1H), 4.27(m, 1H), 4.09(m, fluorobenzonitrile 1H), 3.47-3.30(m,2H), 2.50(m, 3H), 2.13(br, 1H), 1.77(br, 1H), 1.70(m, 5H), 1.40(m, 2H),0.97(t, 3H) 295 (R)-N-{1-[6-butyl-2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ7.98-7.92(d, 1H), methylphenylamino)pyrimidin-4- 7.65(m, 1H), 7.43(m,1H), 6.56-6.43(d, 1H), 4.63- yl]piperidin-3-yl}acetamide 4.25(m, 1H),4.05(m, 1H), 3.94(m, 1H), 3.65- hydrochloride 3.21(m, 2H), 2.68(m, 2H),2.51(d, 3H), 2.10(s, 3H), 2.06-1.94(m, 2H), 1.76(m, 4H), 1.48(m, 2H),0.96(t, 3H) 296 (S)-5-[4-(3-ethylaminopiperidin- ¹H-NMR(400 MHz, CD₃OD)δ 7.90(s, 1H), 7.63(m, 1-yl)-6-propylpyrimidin-2- 1H), 7.48(m, 1H),6.61(s, 1H), 4.53(br, 1H), 4.09(br, ylamino]-2-methylbenzonitrile 1H),3.60(br, 1H), 3.03(m, 2H), 2.66(m, 2H), 2.54(s, dihydrochloride 3H),2.24(m, 1H), 2.00(m, 1H), 1.80(m, 4H), 1.24(m, 3H), 1.06(t, 3H) 2975-[4-(3-ethylaminopiperidin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ 7.90(s, 1H),7.62(m, 6-propylpyrimidin-2-ylamino]-2- 1H), 7.48(m, 1H), 6.60(s, 1H),4.51(br, 1H), 4.33- methylbenzonitrile 4.01(m, 1H), 3.68(m, 1H), 3.56(m,1H), 3.36(m, 1H), dihydrochloride 3.05(m, 2H), 2.67(m, 2H), 2.54(s, 3H),2.38(m, 1H), 1.95(m, 1H), 1.78(m, 4H), 1.26(m, 3H), 1.07(t, 3H) 298N-{1-[6-butyl-2-(3-cyano-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.15(s, 1H),7.46(d, methylphenylamino)pyrimidin-4- 1H), 7.18(d, 1H), 6.99(s, 1H),6.00(s, 1H), 5.70(m, yl]piperidin-3-yl}acetamide 1H), 4.00-3.93(m, 2H),3.73(m, 1H), 3.47(m, 1H), hydrochloride 3.35(m, 1H), 2.50(m, 5H),1.96(s, 4H), 1.76(m, 1H), 1.65(m, 4H), 1.39(m, 2H), 0.94(t, 3H)

TABLE 1-32 Example Compound NMR Spectrum 299 (R)-5-({4-butyl-6-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.15(s, 1H), 7.47(d, (ethylamino)piperidin-1-1H), 7.17(d, 1H), 7.10(brs, 1H), 5.96(s, 1H), 4.32(m,yl]pyrimidin-2-yl}amino)-2- 1H), 4.06(m, 1H), 3.06(m, 1H), 2.89(m, 1H),2.73(m, methylbenzonitrile 2H), 2.66(m, 1H), 2.49(s + m, 3 + 2H),2.04(m, 2H), 1.82(m, 2H), 1.63(m, 2H), 1.56(m, 1H), 1.39(m, 3H), 1.13(t,3H), 0.95(t, 3H) 300 (R)-5-({4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.11(s, 1H), 7.52(d, (butylamino)piperidin-1- 1H), 7.17(d, 1H),7.07(brs, 1H), 5.95(s, 1H), 4.35(m, yl]pyrimidin-2-yl}amino)-2- 1H),4.13(m, 1H), 3.09(m, 1H), 2.85(m, 1H), 2.71- methylbenzonitrile 2.47(m,3H), 2.52-2.48(s + m, 3 + 2H), 2.04(m, 2H), 1.69(m, 4H), 1.67(m, 1H),1.65(m, 1H), 1.49- 1.26(m, 7H), 0.95(t, 3H), 0.91(t, 3H) 301(R)-5-({4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.10(s, 1H), 7.53(d,(pentylamino)piperidin-1- 1H), 7.19(d, 1H), 7.17(brs, 1H), 5.95(s, 1H),4.35(m, yl]pyrimidin-2-yl}amino)-2- 1H), 4.11(m, 1H), 3.07(m, 1H),2.88(m, 1H), 2.72- methylbenzonitrile 2.62(m, 3H), 2.52-2.47(s + m, 3 +2H), 2.00(m, 2H), 1.79(m, 2H), 1.68(m, 3H), 1.51(m, 3H), 1.45(m, 3H),1.29(m, 5H), 0.95(t, 3H), 0.89(t, 3H) 302 (R)-5-({4-butyl-6-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.10(s, 1H), 7.53(d,(isobutylamino)piperidin-1- 1H), 7.45(br, 1H), 7.18(d, 1H), 5.95(s, 1H),4.28(m, yl]pyrimidin-2-yl}amino)-2- 1H), 4.01(m, 1H), 3.10(m, 1H),2.97(m, 1H), 2.65(m, methylbenzonitrile 1H), 2.54-2.48(m, 7H), 2.30(br,3H), 2.09(m, 2H), 1.83(m, 1H), 1.73(m, 3H), 1.71(m, 1H), 1.46(m, 3H),1.00(t, 3H), 0.91(m, 6H) 303 (R)-5-({4-butyl-6-[3- ¹H-NMR(400 MHz,CDCl₃) δ 8.11(s, 1H), 7.51(m, (isopentylamino)piperidin-1- 1H), 7.18(d,1H), 7.08(br, 1H), 5.95(s, 1H), 4.25(m, yl]pyrimidin-2-yl}amino)-2- 1H),4.11(m, 1H), 3.08(m, 1H), 2.90(m, 1H), 2.72- methylbenzonitrile 2.62(m,3H), 2.52-2.47(m, 5H), 2.00(m, 2H), 1.82(m, 1H), 1.71-1.58(m, 6H),1.39(m, 5H), 1.00(t, 3H), 0.90(m, 6H) 304 (R)-5-({4-butyl-6-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.07(s, 1H), 7.57(d,(neopentylamino)piperidin-1- 1H), 7.45(br, 1H), 7.18(d, 1H), 5.94(s,1H), 4.30(m, yl]pyrimidin-2-yl}amino)-2- 1H), 4.15(m, 1H), 3.09(m, 1H),2.89(m, 1H), 2.55(m, methylbenzonitrile 1H), 2.54-2.43(m, 6H), 2.09(m,2H), 1.81(m, 1H), 1.67(m, 2H), 1.56(m, 1H), 1.43(m, 3H), 0.95(t, 3H),0.89(s, 9H) 305 (R)-5-{[4-butyl-6-(3-{[3- ¹H-NMR(400 MHz, CDCl₃) δ8.16(s, 1H), 7.54(br, (methylthio)propyl]amino}piperidin- 1H), 7.48(d,1H), 7.18(d, 1H), 5.95(s, 1H), 4.35(m, 1-yl)pyrimidin-2-yl]amino}-2-1H), 4.00(m, 1H), 3.55(m, 1H), 2.95(m, methylbenzonitrile 1H), 2.79(m,2H), 2.65(m, 1H), 2.53(m, 2H), 2.50(m, 5H), 2.09(s, 3H), 2.00(m, 2H),1.80(m, 4H), 1.65(m, 2H), 1.59(m, 1H), 1.44(m, 3H), 0.95(t, 3H) 306(R)-4-fluoro-N¹-{4-[3- ¹H-NMR (400 MHz, CD₃OD) δ 7.88-7.81(m, 1H),(methylamino)piperidin-1-yl]-6- 7.64(m, 1H), 7.48(m, 1H), 6.71-6.61(m,1H), 4.43- propylpyrimidin-2-yl}benzene- 4.39(m, 1H), 3.97-3.85(m, 1H),3.68(m, 1H), 1,3-diamine dihydrochloride 3.43(m, 1H), 2.80(m, 1H),2.70(m, 2H), 2.61(s, 2H), 2.25(m, 1H), 1.99(m, 2H), 1.81(m, 3H), 1.05(t,3H) 307 (R)-4-chloro-N¹-{4-[3- ¹H-NMR (400 MHz, CD₃OD) δ 7.59-7.52(m,2H), (methylamino)piperidin-1-yl]-6- 7.38(m,1H), 6.68-6.60(m, 1H),4.43-4.29(m, 1H), propylpyrimidin-2-yl}benzene- 3.94-3.85(m, 1H),3.67(m,1H), 3.39(m, 1H), 2.81(s, 1,3-diamine dihydrochloride 1H),2.68(m, 2H), 2.62(s, 2H), 2.24(m, 1H), 1.99(m, 2H), 1.79(m, 3H), 1.06(t,3H)

TABLE 1-33 Example Compound NMR Spectrum 308 (R)-2-amino-5-({4-[3-¹H-NMR (400 MHz, CD₃OD) δ 7.64-7.55(m, 1H),(methylamino)piperidin-1-yl]-6- 7.46-7.30(m, 1H), 7.02-6.92(m, 1H),6.61-6.53(m, propylpyrimidin-2- 1H), 4.33(m, 1H), 3.87(m, 1H), 3.65(m,1H), 3.50(m, yl}amino)benzonitrile 1H), 2.80(s, 1H), 2.66-2.61(m, 4H),2.22(m, 1H), dihydrochloride 2.00(m, 2H), 1.77(m, 3H), 1.04(t, 3H) 309(R)-N-(3-methoxy-4- ¹H-NMR (400 MHz, CD₃OD) δ 7.19-7.11(m, 1H),methylphenyl)-4-[3- 6.98-6.90(m, 2H), 6.59-6.53(m, 1H), 4.44-4.41(m,(methylamino)piperidin-1-yl]-6- 1H), 4.29-4.04(m, 1H), 3.84(s, 3H),3.75-3.50(m, propylpyrimidin-2-amine 1H), 2.80(s, 1H), 2.63(m, 2H),2.51(s, 2H), dihydrochloride 2.19(s + m, 3 + 1H), 1.89(m, 2H), 1.76(m,3H), 1.05(t, 3H) 310 (R)-4-methyl-N¹-{4-[3- ¹H-NMR (400 MHz, CD₃OD) δ7.66-7.60(m, 1H), (methylamino)piperidin-1-yl]-6- 7.56-7.51(m, 2H),7.47(m, 1H), 7.38(m, 1H), 6.67- propylpyrimidin-2-yl}benzene- 6.59(m,1H), 4.38(m, 1H), 4.00-3.95(m, 1H), 1,3-diamine dihydrochloride 3.82(m,1H), 3.40(m, 1H), 2.80(m, 1H), 2.68(m, 2H), 2.58(s, 2H), 2.44(m, 5H),2.23(m, 1H), 1.92(m, 2H), 1.79(m, 3H), 1.06(t, 3H) 311(R)-5-({4-butyl-6-[3- ¹H-NMR (400 MHz, CD₃OD) δ 7.88(s, 1H), 7.65(m,(methylamino)piperidin-1- 1H), 7.48(m, 1H), 6.61(s, 1H), 4.41(m, 1H),3.88(m, yl]pyrimidin-2-yl}amino)-2- 1H), 3.61(m, 1H), 2.79-2.63(m, 5H),2.54(s, 3H), methylbenzonitrile 2.23(m, 1H), 1.98-1.94(m, 2H), 1.74(m,3H), dihydrochloride 1.48(m, 2H), 1.00(t, 3H) 312 (R)-5-({4-butyl-6-[3-¹H-NMR (400 MHz, CD₃OD) δ 7.97(m, 1H), 7.82(m, (methylamino)piperidin-1-1H), 7.67(m, 1H), 7.51(m, 1H), 6.62(m, 1H), 4.44-yl]pyrimidin-2-yl}amino)-2- 4.31(m, 1H), 3.88(m, 1H), 3.76(m, 1H),3.61(m, fluorobenzonitrile 1H), 2.78(s, 1H), 2.70(m, 2H), 2.64(s, 2H),2.23(m, dihydrochloride 1H), 1.98-1.90(m, 2H), 1.74(m, 3H), 1.48(m, 2H),1.00(t, 3H) 313 (R)-N¹-{4-butyl-6-[3- 1H-NMR (400 MHz, CD₃OD) δ8.07-7.71(m, 1H), (methylamino)piperidin-1- 7.62(m, 1H), 7.30(m, 1H),6.66(m, 1H), 4.37(m, 1H), yl]pyrimidin-2-yl}-5- 4.12-4.07(m, 1H),4.00-3.96(m, 1H), 3.59(m, 1H), (trifluoromethyl)benzene-1,3-2.81-2.73(m, 3H), 2.59(m, 2H), 2.26(m, 1H), diamine dihydrochloride1.99(m, 2H), 1.76(m, 3H), 1.49(m, 2H), 1.01(t, 3H) 314(R)-N¹-{4-butyl-6-[3- ¹H-NMR (400 MHz, CD₃OD) δ 7.99-7.60(m, 1H),(methylamino)piperidin-1- 7.58(m, 1H), 7.32-7.19(m, 1H), 6.65(m, 1H),4.34- yl]pyrimidin-2-yl}-3- 4.23(m, 1H), 3.95(m, 1H), 3.77-3.61(m, 2H),2.80(s, (trifluoromethyl)benzene-1,4- 1H), 2.68(m, 2H), 2.53(s, 2H),2.21(m, 1H), 1.73(m, diamine dihydrochloride 2H), 1.47(m, 3H), 1.47(m,2H), 1.00(t, 3H) 315 (R)-3-amino-5-({4-butyl-6-[3- ¹H-NMR (400 MHz,CD₃OD) δ 7.86-7.62(m, 2H), (methylamino)piperidin-1- 7.33(m, 1H),6.93-6.65(m, 1H), 4.56-4.33(m, 1H), yl]pyrimidin-2- 3.93(m, 1H), 3.60(m,1H), 3.45(m, 1H), 2.81- yl}amino)benzonitrile 2.69(m, 5H), 2.25(m, 1H),2.00-1.86(m, 2H), dihydrochloride 1.75(m, 3H), 1.24(m, 2H), 1.01(t, 3H)316 (R)-2-amino-5-({4-butyl-6-[3- ¹H-NMR (400 MHz, CD₃OD) δ 7.75-7.62(m,1H), (methylamino)piperidin-1- 7.55(m, 1H), 7.15(m, 1H), 6.65-6.55(m,1H), yl]pyrimidin-2- 4.36(m, 1H), 3.86(m, 1H), 3.63(m, 1H), 3.50(m, 1H),yl}amino)benzonitrile 2.80(s, 1H), 2.68(m, 2H), 2.62(s, 2H), 2.23(m,1H), dihydrochloride 1.91(m, 2H), 1.72(m, 3H), 1.25(m, 2H), 1.00(t, 3H)

TABLE 1-34 Example Compound NMR Spectrum 317 (R)-N¹-{4-butyl-6-[3-¹H-NMR (400 MHz, CD₃OD) δ 7.64(m, 1H), 7.46- (methylamino)piperidin-1-7.38(m, 2H), 6.65-6.59(m, 1H), 4.39-4.31(m, 1H), yl]pyrimidin-2-yl}-4-3.95-3.83(m, 1H), 3.68(m, 1H), 3.53-3.38(m, 1H),fluorobenzene-1,3-diamine 2.81(s, 1H), 2.70(m, 2H), 2.60(s, 2H), 2.24(m,1H), dihydrochloride 1.98(m, 2H), 1.74(m, 3H), 1.48(m, 2H), 1.01(t, 3H)318 (R)-4-butyl-N-(3-methoxy-4- ¹H-NMR (400 MHz, CD₃OD) δ 7.27-7.18(m,1H), methylphenyl)-6-[3- 6.97-6.85(m, 2H), 6.53(br, 1H), 4.53-4.52(m,1H), (methylamino)piperidin-1- 4.27(m, 1H), 3.95(m, 4H), 3.67(m, 1H),2.81(m, 1H), yl]pyrimidin-2-amine 2.69(m, 2H), 2.52(m, 2H), 2.19(m, 4H),1.91(m, 2H), dihydrochloride 1.73(m, 3H), 1.23(m, 2H), 1.01(t, 3H) 319(R)-N¹-{4-butyl-6-[3- ¹H-NMR (400 MHz, CD₃OD) δ 7.65-7.60(m, 1H),(methylamino)piperidin-1- 7.54(m, 1H), 7.45(m, 1H), 6.67-6.59(m, 1H),yl]pyrimidin-2-yl}-4- 4.36(m, 1H), 4.10-3.96(m, 1H), 3.82(m, 1H), 3.68-methylbenzene-1,3-diamine 3.45(m, 1H), 2.80(s, 1H), 2.70(m, 2H), 2.58(s,2H), dihydrochloride 2.42(s, 3H), 2.23(m, 1H), 1.98(m, 2H), 1.74(m, 3H),1.24(m, 2H), 1.00(t, 3H) 320 (R)-4-butyl-N-[4-fluoro-3- ¹H-NMR (400 MHz,CD₃OD) δ 8.06-7.72(m, 2H), (trifluoromethyl)phenyl]-6-[3- 7.45(m, 1H),6.66-6.61(m, 1H), 4.31(m, 1H), 3.65- (methylamino)piperidin-1- 3.81(m,1H), 3.69(m, 1H), 3.49(m, 1H), 2.80(s, 1H), yl]pyrimidin-2-amine 2.71(m,2H).2.55(s, 2H), 2.24(m, 1H), 1.92(m, 2H), dihydrochloride 1.48(m, 3H),1.29(m, 2H), 1.00(t, 3H) 321 (R)-N¹-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ8.38(s, 1H), 7.39(d, (methylamino)piperidin-1-yl]-6- 1H), 7.05(d, 1H),6.56(s, 1H), 4.38(br, 1H), 3.85(br, propylpyrimidin-2-yl}-3- 1H),3.86(br, 1H), 2.75-7.65(m, 5H), 2.41(m, 1H), nitrobenzene-1,4-diamine2.01-1.88(m, 2H), 1.66(m, 3H), 1.05(t, 3H) dihydrochloride 322(R)-N-(3,4-dimethylphenyl)-4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.21-7.17(m,3H), (methylamino)piperidin-1-yl]-6- 6.59-6.51(m, 1H), 4.34-4.05(m, 2H),3.75(br, 1H), propylpyrimidin-2-amine 3.48-3.31(m, 1H), 2.80(s, 1H),2.64(m, 2H), 2.50(s, dihydrochloride 2H), 2.29(d, 6H), 2.20(m, 1H),1.90(m, 2H), 1.77(m, 3H), 1.05(t, 3H) 323(R)-N-(3-fluoro-4-methylphenyl)- ¹H-NMR(400 MHz, CD₃OD) δ 7.33-7.27(m,2H), 4-[3-(methylamino)piperidin-1- 7.15(d, 1H), 6.58(s, 1H), 4.41(br,1H), 3.86(m, 1H), yl]-6-propylpyrimidin-2-amine 3.64(m, 1H), 2.78(m,1H), 2.64(m, 4H), 2.26(s, 3H), dihydrochloride 2.60(br, 1H), 1.81(m,2H), 1.77(m, 3H), 1.05(t, 3H) 324 (R)-N-[4-methyl-3- ¹H-NMR(400 MHz,CD₃OD) δ 8.01-7.77(m, 1H), (trifluoromethyl)phenyl]-4-[3- 7.65-7.43(m,2H), 6.66-6.59(m, 1H), 4.35-4.26(m, (methylamino)piperidin-1-yl]-6- 1H),4.11-3.98(m, 1H), 3.79-3.64(m, 2H), 2.80(s, propylpyrimidin-2-amine 1H),2.67(m, 2H), 2.51-2.48(m, 5H), 2.23(m, 1H), dihydrochloride 1.91(m, 2H),1.78(m, 3H), 1.06(t, 3H) 325 (R)-4-methoxy-N¹-{4-[3- ¹H-NMR(400 MHz,CD₃OD) δ 7.67-7.63(m, 1H), (methylamino)piperidin-1-yl]-6- 7.56(m, 1H),7.40-7.30(m, 1H), 6.65-6.56(m, 1H), propylpyrimidin-2-yl}benzene-4.30(m, 1H), 4.03-4.00(s + m, 3 + 1H), 3.78-3.71(m, 1,3-diaminedihydrochloride 2H), 2.80(s, 1H), 2.67(m, 2H), 2.56(s, 2H), 2.26(m, 1H),1.90(m, 2H), 1.78(m, 3H), 1.05(t, 3H) 326 (R)-N-{4-[3- ¹H-NMR(400 MHz,CD₃OD) δ 8.43(m, 1H), 7.94(m, (methylamino)piperidin-1-yl]-6- 2H),7.36(m, 1H), 6.70-6.61(m, 1H), 4.40(m, 1H),propylpyrimidin-2-yl}-1H-indazol- 4.03(m, 1H), 3.84(m, 1H), 3.72(m, 1H),3.60(m, 1H), 6-amine dihydrochloride 2.82(s, 1H), 2.69(m, 2H), 2.51(s,2H), 2.23(m, 1H), 1.98(m, 2H), 1.80(m, 3H), 1.06(t, 3H)

TABLE 1-35 Example Compound NMR Spectrum 327 (R)-N⁴-{4-[3- ¹H-NMR(400MHz, CD₃OD) δ 6.89(m, 2H), 6.73(m, (methylamino)piperidin-1-yl]-6- 1H),6.49(s, 1H), 4.28(m, 1H), 3.91(m, 2H), 3.65(m,propylpyrimidin-2-yl}benzene- 1H), 2.63(s, 4H), 2.21(m, 1H), 1.88(m,2H), 1.76(m, 1,2,4-triamine 3H), 1.04(t, 3H) 328 (R)-N¹-{4-butyl-6-[3-¹H-NMR(400 MHz, CD₃OD) δ 8.38(s, 1H), 7.40(d, (methylamino)piperidin-1-1H), 7.05(d, 1H), 6.55(s, 1H), 4.39(m, 1H), 3.85(m,yl]pyrimidin-2-yl}-3- 2H), 3.65(m, 1H), 2.68(m, 4H), 2.23(m, 1H),1.90(m, nitrobenzene-1,4-diamine 2H), 1.71(m, 3H), 1.47(m, 2H), 1.00(t,3H) dihydrochloride 329 (R)-3-({4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ7.98(s, 1H), 7.79(m, (methylamino)piperidin-1- 1H), 7.61(m, 2H), 6.64(s,1H), 4.45(m, 1H), 3.91(m, yl]pyrimidin-2- 1H), 3.78(m, 1H), 3.61(m, 1H),3.40(m, 1H), 2.79(m, yl}amino)benzonitrile 1H), 2.71(m, 2H), 2.63(m,2H), 2.24(m, 1H), 1.95- dihydrochloride 1.86(m, 2H), 1.75(m, 3H),1.48(m, 2H), 1.01(t, 3H) 330 (R)-4-butyl-N-(3,4- ¹H-NMR(400 MHz, CD₃OD)δ 7.21-7.17(m, 3H), dimethylphenyl)-6-[3- 6.58-6.51(m, 1H), 4.38-4.22(m,1H), 4.11-4.04(m, (methylamino)piperidin-1- 1H), 3.75(m, 1H), 3.61(m,1H), 2.81(s, 1H), 2.67(m, yl]pyrimidin-2-amine 2H), 2.51(m, 2H), 2.29(m,7H), 2.00(m, 2H), 1.72(m, dihydrochloride 3H), 1.46(m, 2H), 1.00(t, 3H)331 (R)-4-butyl-N-(3-fluoro-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.31(m, 2H),7.18(m, methylphenyl)-6-[3- 1H), 6.64-6.57(m, 1H), 4.45-4.36(m, 1H),3.88(m, (methylamino)piperidin-1- 1H), 3.65(m,1H), 2.80(s, 1H), 2.69(m,2H), 2.61(m, yl]pyrimidin-2-amine 2H), 2.26(s + m, 3 + 1H), 1.92(m, 2H),1.73(m, 3H), dihydrochloride 1.46(m, 2H), 1.00(t, 3H) 332(R)-4-butyl-N-[4-methyl-3- ¹H-NMR(400 MHz, CD₃OD) δ 7.87(brs, 1H),7.59(m, (trifluoromethyl)phenyl]-6-[3- 1H), 7.46(m, 1H), 6.60(s, 1H),4.30(m, 1H), 3.86(br, (methylamino)piperidin-1- 2H), 3.63(m, 1H),2.70(m, 2H), 2.48(m, 2H), 2.23(s, yl]pyrimidin-2-amine 3H), 2.23(m, 1H),1.89(m, 2H), 1.73(m, 3H), 1.48(m, dihydrochloride 2H), 1.00(t, 3H) 333(R)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) 7.60-7.53(m, 2H),(methylamino)piperidin-1- 7.39(m, 1H), 7.31(m, 1H), 6.65-6.56(m, 1H),yl]pyrimidin-2-yl}-4- 4.31(m, 1H), 4.32(m, 3 + 1H), 3.79-3.71(m, 2H),methoxybenzene-1,3-diamine 2.80(s, 1H), 2.71(m, 2H), 2.56(s, 2H),2.23(br, 1H), dihydrochloride 1.99(m, 2H), 1.74(m, 3H), 1.47(m, 2H),0.99(t, 3H) 334 (R)-N-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ8.48-8.42(m, 1H), (methylamino)piperidin-1- 8.06-7.93(m, 2H), 7.36(m,1H), 6.71-6.61(m, 1H), yl]pyrimidin-2-yl}-1H-indazol-6- 4.41(m, 1H),4.09(m, 1H), 3.84(m, 1H), 3.71(m, 1H), amine dihydrochloride3.61-3.39(m, 1H), 2.82(m, 1H), 2.71(m, 2H), 2.54(s, 2H), 2.26(m, 1H),1.99(m, 2H), 1.76(m, 3H), 1.47(m, 2H), 1.00(t, 3H) 335(R)-N⁴-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 6.85(s, 1H), 6.78(d,(methylamino)piperidin-1- 1H), 6.66(d, 1H), 6.46(s, 1H), 4.25(d, 1H),3.89(m, yl]pyrimidin-2-yl}benzene-1,2,4- 2H), 3.63(m, 1H), 2.64(m, 5H),2.20(m, 1H), 1.88(m, triamine 2H), 1.68(m, 3H), 1.45(m, 2H), 0.98(t, 3H)336 (R)-4-(3-aminopiperidin-1-yl)-6- ¹H-NMR(400 MHz, CD₃OD) δ 8.30(brs,1H), 8.25(s, butyl-N-(3-nitrophenyl)pyrimidin- 1H), 7.78(m, 2H), 7.06(s,1H), 4.59(br, 1H), 4.14(br, 2-amine dihydrochloride 1H), 3.74-3.48(br,3H), 2.74(m, 2H), 2.22(br, 1H), 2.01(br, 1H), 1.87-1.72(m, 4H), 1.46(m,2H), 0.99(t, 3H)

TABLE 1-36 Example Compound NMR Spectrum 337(R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.50-8.46(m,1H), yl)-6-butylpyrimidin-2-yl]-3- 7.36(d, 1H), 7.05(d, 1H),6.55-6.47(m, 1H), 4.45- nitrobenzene-1,4-diamine 4.22(m, 1H), 4.03(m,1H), 3.43(m, 3H), 2.68(m, dihydrochloride 2H), 2.20(m, 1H), 1.97(m, 1H),1.72(m, 4H), 1.46(m, 2H), 1.00(t, 3H) 338(R)-4-(3-aminopiperidin-1-yl)-6- ¹H-NMR(400 MHz, CD₃OD) δ 8.61(m, 1H),7.72(m, butyl-N-(4-fluoro-3- 1H), 7.51(t, 1H), 6.62(br, 1H),4.75-3.92(m, 2H), nitrophenyl)pyrimidin-2-amine 3.48(m, 3H), 2.72(t,2H), 2.21(m, 1H), 1.97(m, 1H), dihydrochloride 1.75(m, 4H), 1.48(m, 2H),0.99(t, 3H) 339 (R)-4-(3-aminopiperidin-1-yl)-6- ¹H-NMR(400 MHz, CD₃OD)δ 8.52(s, 1H), 7.58(m, butyl-N-(4-methyl-3- 1H), 7.50(m, 1H),6.36-6.58(m, 1H), 4.46-4.08(m, nitrophenyl)pyrimidin-2-amine 2H),3.64-3.54(m, 3H), 2.72(m, 2H), 2.52(m, 3H), dihydrochloride 2.22(m, 1H),1.98(m, 1H), 1.76(m, 4H), 1.47(m, 2H), 1.01(t, 3H) 340(R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.10-7.77(m,1H), yl)-6-butylpyrimidin-2-yl]-3- 7.83-7.67(m, 1H), 7.49-7.40(m, 1H),7.32-6.97(m, (trifluoromethyl)benzene-1,4- 1H), 6.59(m, 1H),4.58-3.93(m, 2H), 3.63-3.35(m, diamine dihydrochloride 3H), 2.70(m, 2H),2.19(m,1H), 1.94(m, 1H), 1.82(m, 4H), 1.46(m, 2H), 1.00(t, 3H) 341(R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.16(d, 1H),7.75(d, yl)-6-butylpyrimidin-2-yl]-5- 1H), 7.46(s, 1H), 6.97-6.92(m,1H), 6.65(m, 1H), (trifluoromethyl)benzene-1,3- 4.67-3.97(m, 2H),3.70-3.59(m, 3H), 2.74(m, 2H), diamine dihydrochloride 2.20(m, 1H),1.96(m, 1H), 1.83(m, 4H), 1.48(m, 2H), 1.01(t, 3H) 342(R)-3-amino-5-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.00(m, 1H), 7.77(m,aminopiperidin-1-yl)-6- 1H), 7.42(s, 1H), 6.95(m, 1H), 6.67(m, 1H),4.69- butylpyrimidin-2- 3.98(m, 2H), 3.63-3.48(m, 3H), 2.73(m, 2H),yl]amino}benzonitrile 2.19(m, 1H), 1.98(m, 1H), 1.48(m, 4H), 1.17(m,2H), dihydrochloride 1.01(t, 3H) 343 (R)-4-(3-aminopiperidin-1-yl)-6-¹H-NMR(400 MHz, CD₃OD) δ 8.03-7.77(m, 1H), butyl-N-[4-methyl-3-7.71-7.43(m, 2H), 6.60(m, 1H), 4.56-3.96(m, 2H),(trifluoromethyl)phenyl]pyrimidin- 3.50(m, 3H), 2.71(m, 2H), 2.48(s,3H), 2.20(m, 1H), 2-amine dihydrochloride 2.00(m, 1H), 1.95-1.75(m, 4H),1.47(m, 2H), 1.01(t, 3H) 344 (R)-4-(3-aminopiperidin-1-yl)-6- ¹H-NMR(400MHz, CD₃OD) δ 7.27(m, 2H), 7.17(m, butyl-N-(3-fluoro-4- 1H), 6.55(s,1H), 4.57-4.10(m, 2H), 3.61-3.48(m, methylphenyl)pyrimidin-2-amine 3H),2.68(m, 2H), 2.27(s, 3H), 2.19(m, 1H), 1.93(m, dihydrochloride 1H),1.82-1.71(m, 4H), 1.45(m, 2H), 1.00(t, 3H) 345(R)-4-(3-aminopiperidin-1-yl)-6- ¹H-NMR(400 MHz, CD₃OD) δ 7.16(d, 1H),7.05(br, butyl-N-(3-methoxy-4- 1H), 6.93(m, 1H), 6.51(s, 1H),4.46-4.22(m, 2H), methylphenyl)pyrimidin-2-amine 3.59-3.48(m, 3H),2.67(t, 2H), 2.19(s + m, 3 + 1H), dihydrochloride 1.91(m, 1H),1.81-1.70(m, 4H), 1.45(m, 2H), 1.00(t, 3H) 346(R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.73-7.59(m,1H), yl)-6-butylpyrimidin-2-yl]-4- 7.56-7.45(m, 2H), 7.42-7.30(m, 1H),6.60(m, 1H), methylbenzene-1,3-diamine 4.64-3.94(m, 2H), 3.65-3.49(m,3H), 2.71(m, 2H), dihydrochloride 2.42(s, 3H), 2.18(m, 1H), 1.94(m, 1H),1.81(m, 4H), 1.46(m, 2H), 1.00(t, 3H)

TABLE 1-37 Example Compound NMR Spectrum 347(R)-4-(3-aminopiperidin-1-yl)-6- ¹H-NMR(400 MHz, CD₃OD) δ 7.20(m, 3H),6.51(s, butyl-N-(3,4- 1H), 4.58-3.94(m, 2H), 3.61-3.58(m, 3H), 2.67(t,dimethylphenyl)pyrimidin-2- 2H), 2.29-2.27(s + s, 6H), 2.18(m, 1H),1.92(m, 1H), amine dihydrochloride 1.82-1.71(m, 4H), 1.46(m, 2H),1.00(t, 3H) 348 (R)-4-(3-aminopiperidin-1-yl)-6- ¹H-NMR(400 MHz, CD₃OD)δ 7.94(m, 1H), 7.77(m, butyl-N-[4-fluoro-3- 1H), 7.43(t, 1H), 6.58(3,1H), 4.40-4.16(m, 2H), (trifluoromethyl)phenyl]pyrimidin- 3.50(m, 3H),2.70(t, 2H), 2.18(m, 1H), 1.91(m, 1H), 2-amine dihydrochloride 1.76(m,4H), 1.46(m, 2H), 1.00(t, 3H) 349 (R)-N¹-[4-(3-aminopiperidin-1-¹H-NMR(400 MHz, CD₃OD) δ 7.74-7.64(m, 1H), yl)-6-butylpyrimidin-2-yl]-4-7.51(m, 1H), 7.42(m, 1H), 7.19-6.77(m, 1H), 6.61-fluorobenzene-1,3-diamine 6.55(m, 1H), 4.64-3.95(m, 2H), 3.63-3.48(m,3H), dihydrochloride 2.70(m, 2H), 2.18(m, 1H), 1.95(m,1H), 1.80(m, 4H),1.48(m, 2H), 1.00(t, 3H) 350 (R)-2-amino-5-{[4-(3- ¹H-NMR(400 MHz,CD₃OD) δ 7.71-7.53(m, 1H), aminopiperidin-1-yl)-6- 7.38(s, 1H), 7.15(m,1H), 6.55(m, 1H), 4.59- butylpyrimidin-2- 3.93(m, 2H), 3.61-3.48(m, 3H),2.68(m, 2H), yl]amino}benzonitrile 2.18(m, 1H), 1.94(m, 1H), 1.73(m,4H), 1.45(m, 2H), dihydrochloride 1.00(t, 3H) 351(R)-3-{[4-(3-aminopiperidin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ 7.84(m, 1H),7.75- 6-butylpyrimidin-2- 7.70(m, 3H), 7.04(s, 1H), 4.60-4.13(m, 2H),3.74- yl]amino}benzonitrile 3.53(m, 3H), 2.73(m, 2H), 2.21(m, 1H),1.99(m, 1H), dihydrochloride 1.85-1.72(m, 4H), 1.47(m, 2H), 0.99(t, 3H)352 (R)-N¹-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.23(m, 2H),7.54(m, yl)-6-butylpyrimidin-2- 2H), 6.62(br, 1H), 4.64-3.97(m, 2H),3.63-3.54(m, yl]benzene-1,4-diamine 3H), 2.72(m, 2H), 2.20(m, 1H),1.96(m, 1H), 1.85- dihydrochloride 1.76(m, 4H), 1.46(m, 2H), 1.00(t, 3H)353 (R)-4-(3-aminopiperidin-1-yl)-6- ¹H-NMR(400 MHz, CD₃OD) δ 8.46(br,1H), 7.71(m, butyl-N-(4-chloro-3- 2H), 6.64(br, 1H) 4.42-4.02(m, 2H),3.65(m, 3H), nitrophenyl)pyrimidin-2-amine 2.73(m, 2H), 2.23(m, 1H),1.99(m, 1H), 1.76(m, 4H), dihydrochloride 1.49(m, 2H), 1.01(t, 3H) 354(R)-N⁴-[4-(3-aminopiperidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 6.93(s, 1H),6.69(s, yl)-6-butylpyrimidin-2- 2H), 6.23(s, 1H), 4.39(d, 1H), 3.97(m,1H), 3.44- yl]benzene-1,2,4-triamine 3.35(m, 3H), 2.54(m, 2H), 2.14(m,1H), 1.87(m, 1H), 1.73-1.65(m, 4H), 1.42(m, 2H), 0.97(t, 3H)

Test Example 1 Evaluation of Agonistic Activity in CHO-K1 CellsExpressing Human 5-HT_(4(a))

As CHO-K1 cells stably expressing human 5-HT_(4(a)), we used theGeneBIAzer HTR4-CRE-bla CHO-K1 cells (Invitrogen Corp.). The cells werecultured, under the condition of 37° C. and 5% CO₂, in a DMEMsupplemented with 10% fetal bovine serum (FBS), 25 mM HEPES (pH7.4), 600μg/ml hygromycin B, 0.1 mM non-essential amino acids, 100 unit/mlpenicillin and 100 μg/ml streptomycin. Subcultures were performed threetimes per one week, each being at less than 80% confluence. At theprevious day before treating test compounds, the cells were collectedusing 0.5% trypsin/EDTA and then diluted with a DMEM supplemented with1% FBS, 25 mM HEPES, and 0.1 mM non-essential amino acids into 3.125×10⁵cells/ml. 32 μl of the diluted cells were added into 384-well plate (10⁴cells per well) and then incubated overnight. After the overnightculture, 8 μl of the medium having 1% of DMSO was added into thecell-free control well and the non-stimulating control well,respectively. 8 μl of the respective test compound dilutions (which hadbeen prepared by diluting by 100-times with the medium as mentioned inthe above) having 1% of DMSO were added to the respective remainingwells. After being cultured in the incubator for 5 hours, the wells ofthe 384-plate were treated with the substrate solution (8 μl per well)prepared according to the vendor's instruction (i.e., Invitrogen'sinstruction), and then incubated in the dark room for additional twohours. Agonistic activities on 5-HT₄ receptor were evaluated, on thebasis of fluorescence values of the cleavage-products by beta-lactamase.After exciting to 410 nm of wavelength using a fluorescence detector(Genios Pro), we measured the fluorescence values at two emissionwavelengths (first wavelength: 465 nm, second wavelength: 535 nm). Datawere analyzed on the basis of the ratio of fluorescence intensities ofeach well at the respective wavelengths. Each EC₅₀ value was calculatedby non-linear regression analysis using the “GraphPad Prism” program,based on the activities according to 8-different concentrations of thetest compounds. The results are shown in Table 2-1 and 2-2 below.

TABLE 2-1 Example EC₅₀(nM) 22 0.19 24 0.026 25 0.073 40 0.26 45 0.27 470.15 73 0.24 74 0.063 76 0.061 77 0.084 78 0.12 82 0.096 83 0.36 84 0.2799 0.37 100 0.2 101 0.24 102 0.47 104 0.36 109 0.32 111 0.091 112 0.37114 0.31 117 0.077 118 0.024 119 0.156 120 0.073 121 0.093 122 0.011 1230.121 124 0.028 125 0.051 126 0.013 127 0.053 128 0.0049 129 0.0041 1310.12 136 0.35 138 0.46 140 0.28 141 0.15 142 0.3 146 0.27 147 0.31 1500.07 151 0.361 153 0.02 154 0.041 155 0.093 156 0.066 157 0.088 1580.054 159 0.046 160 0.125 161 0.148 162 0.043 163 0.088 164 0.075 1650.188 174 0.039 175 0.035 176 0.018 177 0.049 178 0.082 179 0.027 1800.153 181 0.025 182 0.022 187 0.24 188 0.43 189 0.32 190 0.46 191 0.34198 0.4 200 0.18 203 0.14 205 0.008 206 0.0087 207 0.013 208 0.029 2090.015 210 0.022 211 0.023 212 0.1 214 0.072 215 0.064 216 0.016 2170.013 218 0.016 219 0.01 220 0.0082 221 0.122 222 0.056 223 0.045 2240.07 225 0.021 226 0.071 227 0.017 228 0.0035 229 0.0041 230 0.0046 2310.0063 232 0.0037 233 0.009 234 0.015 235 0.012 236 0.0088 237 0.014 2380.0083 239 0.017 240 0.012 241 0.014 242 0.0091 243 0.0094 244 0.02 2450.047 246 0.06 247 0.023 248 0.018 249 0.025 250 0.027 251 0.016 2520.094 253 0.057 254 0.038 255 0.016 256 0.012 257 0.042 259 0.084 2600.0075 261 0.105 262 0.021 263 0.0072 264 0.328 265 0.049 266 0.0096 2670.088 268 0.025 269 0.016 270 0.148 271 0.026 272 0.011 273 0.046 2740.006

TABLE 2-2 Example EC₅₀(nM) 275 0.0034 276 0.018 277 0.014 278 0.01 2790.014 282 0.073 283 0.0084 284 0.0032 285 0.005 286 0.0044 287 0.026 2880.0046 289 0.0065 290 0.0041 291 0.0028 292 0.019 293 0.023 294 0.108295 0.0086 296 0.015 297 0.0024 298 0.012 299 0.004 300 0.0097 301 0.019302 0.019 303 0.025 304 0.049 305 0.0091 306 0.015 307 0.004 308 0.013309 0.011 310 0.047 311 0.0026 312 0.014 313 0.005 314 0.0019 315 0.0012316 0.0067 317 0.0066 318 0.025 319 0.0047 320 0.018 321 0.0031 3220.243 323 0.416 324 0.0087 328 0.0029 329 0.054 330 0.086 331 0.218 3320.017 333 0.132 337 0.006 338 0.014 339 0.017 340 0.112 342 0.0041 3430.034 344 0.448 345 0.08 346 0.135 347 0.391 348 0.102 349 0.014 3500.028 352 0.029 353 0.337

As shown in Table 2-1 and 2-2, the compounds of the present inventionhave excellent activities as a 5-HT₄ receptor agonist, and thereforethey can be usefully applied for preventing or treating the dysfunctionin gastrointestinal motility.

The invention claimed is:
 1. A method for agonizing a 5-HT₄ receptor,comprising administering an effective amount of a compound of Formula 1or a pharmaceutically acceptable salt thereof to a subject in needthereof:

wherein, R₁ is a phenyl group substituted with one or more substituentsselected from the group consisting of amino, halogen, cyano, nitro, C₁₋₅alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen),C₁₋₅ alkoxy, C₁₋₅ alkylthio, and aminocarbonyl; or a heteroaryl groupselected from the group consisting of quinolinyl, chromenonyl,benzofuranyl, indolyl, indolinyl, benzimidazolyl, and indazolyl, whereinthe heteroaryl group may be optionally substituted with one or more C₁₋₅alkyl (where the C₁₋₅ alkyl is optionally substituted with halogen), R₂is a nitrogen-containing cyclic group of the following Formula B(where * in Formula B represents the position attached to the compoundof Formula 1),

R₃ is a C₁₋₅ alkyl group, R₄ is hydrogen; a C₁₋₅ alkyl group optionallysubstituted with or a C₁₋₅ alkoxycarbonyl group, R₅ is hydrogen; ahydroxyl group; a benzyloxy group; a C₁₋₅ alkyl group; or a groupselected from the group consisting of the following Formulas E and I(where * in Formulas E and I represents the position attached to one ofthe compound of Formula B),

R₆ is hydrogen, X is —CH(R₇)—; —N(R₈)—; or —O—, R₇ is hydrogen, R₄ andR₅ are optionally joined to each other to form a pentagonal or hexagonalring, R₈ is hydrogen; or a C₁₋₅ alkyl group, R₉ is a C₁₋₁₀ alkyl groupoptionally substituted with hydroxy, R₁₀ is hydrogen, R₁₁ and R₁₂ are,independently each other, hydrogen; or a C₁₋₁₀ alkyl group optionallysubstituted with a substituent selected from the group consisting ofC₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionallysubstituted with hydroxy), thiophenyl, pyrrolyl, and furanyl (where thefuranyl is optionally substituted with mono- or di-C₁₋₅ alkyl)), whereinthe agonizing a 5-HT₄ receptor effects to treat a dysfunction ingastrointestinal motility in a disease selected from the groupconsisting of gastroesophageal reflux disease (GERD), constipation,irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayedgastric emptying, gastroparesis, intestinal pseudo-obstruction,drug-induced delayed transit, and diabetic gastric atony.
 2. The methodof claim 1, wherein, R₁ is a phenyl group substituted with one or moresubstituents selected from the group consisting of amino, halogen,cyano, nitro, C₁₋₃ alkyl (where the C₁₋₃ alkyl is optionally substitutedwith halogen), C₁₋₅ alkoxy, C₁₋₅ alkylthio, and aminocarbonyl; or aheteroaryl group selected from the group consisting of quinolinyl,chromenonyl, benzofuranyl, indolyl, indolinyl, benzimidazol-5-yl,benzimidazol-6-yl, and indazolyl, wherein the heteroaryl group may beoptionally substituted with one or more C₁₋₅ alkyl (where the C₁₋₅ alkylis optionally substituted with halogen), R₂ is a nitrogen-containingcyclic group of the following Formula B (where * in Formula B representsthe position attached to the compound of Formula 1),

R₃ is a C₂₋₅ alkyl group, R₄ is hydrogen; a C₁₋₅ alkyl group optionallysubstituted with hydroxy; or a C₁₋₅ alkoxycarbonyl group, R₅ ishydrogen; a hydroxyl group; a benzyloxy group; a C₁₋₅ alkyl group; or agroup selected from the group consisting of the following Formulas E andI (where * in Formulas E and I represents the position attached to oneof the compound of Formula B),

R₆ is hydrogen, X is —CH(R₇)—; —N(R₈)—; or —O—, R₇ is hydrogen, R₄ andR₅ are optionally joined to each other to form a pentagonal or hexagonalring, R₈ is a C₁₋₅ alkyl group, R₉ is a C₁₋₁₀ alkyl group optionallysubstituted with hydroxy, R₁₀ is hydrogen, R₁₁ and R₁₂ are,independently each other, hydrogen; or a C₁₋₁₀ alkyl group optionallysubstituted with a substituent selected from the group consisting ofC₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionallysubstituted with hydroxy), thiophenyl, pyrrolyl, and furanyl (where thefuranyl is optionally substituted with mono- or di-C₁₋₅ alkyl).
 3. Themethod of claim 1, wherein the compound is selected from the groupconsisting of:N-(4-fluorophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(4-fluorophenyl)-4-morpholino-6-propylpyrimidin-2-amine;N-(4-fluorophenyl)-4-(2-methylpiperidin-1-yl)-6-propylpyrimidin-2-amine;N-(4-fluorophenyl)-4-(3-methylpiperidin-1-yl)-6-propylpyrimidin-2-amine;N-(4-fluorophenyl)-4-(decahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(4-fluorophenyl)-4-(piperazin-1-yl)-6-propylpyrimidin-2-amine;4-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;2-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;ethyl1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-carboxylate;4-butyl-N-(4-fluorophenyl)-6-(piperidin-1-yl)pyrimidin-2-amine;4-butyl-6-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)pyrimidin-2-amine;2-{1-[6-butyl-2-(4-fluorophenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;4-butyl-N-(4-fluorophenyl)-6-morpholinopyrimidin-2-amine;2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-(1-{2-[3-(methylthio)phenylamino]-6-propylpyrimidin-4-yl}piperidin-2-yl)ethanol;N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;4-[3-(benzyloxy)piperidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;N-(3-chloro-4-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;4-(piperidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-amine;N-[3-(methylthio)phenyl]-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(5-methoxy-2-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(5-chloro-2-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(4-fluoro-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(4-methoxyphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(3-methoxyphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(3-chlorophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-(4-chloro-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;3-[4-(piperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;N-(4-methyl-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;2-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;N-(4-morpholino-6-propylpyrimidin-2-yl)-1H-indol-6-amine;N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;(R)-3-[4-(3-ethylmorpholino)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-3-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;4-morpholino-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;N-(4-fluoro-3-nitrophenyl)-4-morpholino-6-propylpyrimidin-2-amine;N-(4-chloro-3-nitrophenyl)-4-morpholino-6-propylpyrimidin-2-amine;N-(3-methoxyphenyl)-4-morpholino-6-propylpyrimidin-2-amine;N-(4-methoxyphenyl)-4-morpholino-6-propylpyrimidin-2-amine;N-[3-(methylthio)phenyl]-4-morpholino-6-propylpyrimidin-2-amine;N-(3-chlorophenyl)-4-morpholino-6-propylpyrimidin-2-amine;N-(3-chloro-4-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;4-morpholino-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;N-(4-morpholino-6-propylpyrimidin-2-yl)-1H-indol-5-amine;N-(4-morpholino-6-propylpyrimidin-2-yl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine;N-(4-morpholino-6-propylpyrimidin-2-yl)quinolin-6-amine;3-(4-morpholino-6-propylpyrimidin-2-ylamino)benzonitrile;N-(5-methoxy-2-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;N-(5-chloro-2-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;N-(4-morpholino-6-propylpyrimidin-2-yl)quinolin-3-amine;4-(2-ethylpiperidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;4-(2-ethylpiperidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine;N-(4-chloro-3-nitrophenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;4-(2-ethylpiperidin-1-yl)-N-(3-methoxyphenyl)-6-propylpyrimidin-2-amine;4-(2-ethylpiperidin-1-yl)-N-(4-methoxyphenyl)-6-propylpyrimidin-2-amine;4-(2-ethylpiperidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine;N-(3-chlorophenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;N-(3-chloro-4-methylphenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;4-(2-ethylpiperidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine;N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;3-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;4-(2-ethylpiperidin-1-yl)-N-(5-methoxy-2-methylphenyl)-6-propylpyrimidin-2-amine;N-(5-chloro-2-methylphenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-3-amine;(R)—N-(4-chloro-3-nitrophenyl)-4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-amine;(R)—N-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;(R)—N-(2-methylpiperazin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;(R)—N-(2-methylpiperazin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;(R)—N-(4-fluoro-3-nitrophenyl)-4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-amine;(R)—N-(4-methyl-3-nitrophenyl)-4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-amine;(R)-4-fluoro-N¹-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine;(R)—N¹-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;(R)-2-fluoro-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-2-methyl-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-2-amino-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)—N¹-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;(R)-3-amino-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-3-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzamide;3-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;2-{1-[2-(1-ethyl-1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(1H-indol-5-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-(1-{6-propyl-2-[2-(trifluoromethyl)-1H-benzo[d]imidazol-6-ylamino]pyrimidin-4-yl}piperidin-2-yl)ethanol;2-{1-[2-(4-methoxyphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(3-methoxyphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(5-methoxy-2-methylphenyamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(2,3-dimethylbenzofuran-5-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[6-propyl-2-(quinolin-6-ylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(3-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;7-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-4-methyl-2H-chromen-2-one;2-{1-[6-propyl-2-(3-trifluoromethylphenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[6-propyl-2-(quinolin-3-ylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;(S)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;(S)-4-(3-aminopiperidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;(S)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;(S)-5-{4-[3-(butylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(S)-5-{4-[3-(pentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(S)-5-{4-[3-(isobutylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(S)-5-{4-[3-(isopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(S)-2-methyl-5-{4-[3-(neopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(S)-5-(4-{3-[(1H-pyrrol-2-yl)methylamino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;(S)-2-methyl-5-(4-propyl-6-{3-[(thiophen-2-ylmethyl)amino]piperidin-1-yl}pyrimidin-2-ylamino)benzonitrile;(S)-5-(4-{3-[(4,5-dimethylfuran-2-ylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;(S)-2-methyl-5-{4-[3-(3-methylthiopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(S)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(S)-5-{4-[3-(4-hydroxybenzylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(S)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;(S)-5-(4-{3-[bis(cyclopropylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;(R)-5-(4-{3-[bis(cyclopropylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;4-ethyl-N-(4-fluorophenyl)-6-(piperidin-1-yl)pyrimidin-2-amine;4-ethyl-N-(4-fluorophenyl)-6-(octahydroquinolin-1(2H)-yl)pyrimidin-2-amine;4-ethyl-6-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)pyrimidin-2-amine;2-{1-[6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;4-ethyl-N-(4-fluorophenyl)-6-morpholinopyrimidin-2-amine;2-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(4-amino-3-trifluoromethylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;2-fluoro-5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;2-amino-5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;2-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;2-{1-[2-(indolin-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;(S)-2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;(S)-2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;(R)-2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;3-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;N-(3-nitrophenyl)-4-(octahydroquinoin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(4-fluoro-3-nitrophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(4-chloro-3-nitrophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(3-methoxyphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(5-methoxy-2-methylphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(4-methoxyphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;4-(octahydroquinolin-1(2H)-yl)-6-propyl-N-(3-trifluoromethylphenyl)pyrimidin-2-amine;N-(3-chlorophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(5-chloro-2-methylphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(3-chloro-4-methylphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-(3-methylthiophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-amine;N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;4-methyl-7-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amino]-2H-chromen-2-one;N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]quinolin-3-amine;(R)-5-{4-[3-(ethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)-5-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)-5-{4-[3-(butylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)-2-methyl-5-{4-[3-(pentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(R)-5-{4-[3-(isobutylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)-5-{4-[3-(isopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)-2-methyl-5-{4-[3-(neopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(R)-5-{4-[3-(isopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)-5-(4-{3-[(1H-pyrrol-2-yl)methylamino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;(R)-2-methyl-5-(4-propyl-6-{3-[(thiophen-2-ylmethyl)amino]piperidin-1-yl}pyrimidin-2-ylamino)benzonitrile;(R)-5-(4-{3-[(4,5-dimethylfuran-2-ylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;(R)-2-methyl-5-{4-[3-(3-methylthiopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(R)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)-5-{4-[3-(cyclopentylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)-5-{4-[3-(4-hydroxybenzylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;(R)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;(R)-3-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(R)-3-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(R)-2-fluoro-5-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(R)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-fluorobenzonitrile;(R)—N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-4-fluorobenzene-1,3-diamine;(R)—N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;(R)-3-amino-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;(R)—N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;(R)—N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine;(R)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[6-butyl-2-(4-methyl-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[6-butyl-2-(4-fluoro-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[6-butyl-2-(4-chloro-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(3-amino-5-trifluoromethylphenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(4-amino-3-trifluoromethylphenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[6-butyl-2-(4-fluoro-3-trifluoromethylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[6-butyl-2-(3-cyano-4-fluorophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(4-amino-3-cyanophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;(R)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;(R)—N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;(R)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;(R)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;(R)—N-(1-{2-[4-fluoro-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;(R)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;(R)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;(R)—N-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;(R)—N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;(R)-2-hydroxy-N-(1-{2-[4-methyl-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;(R)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;(R)-4-(3-aminopiperidin-1-yl)-N-(3-fluoro-4-methylphenyl)-6-propylpyrimidin-2-amine;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;(R)-3-amino-5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}benzonitrile;(R)-2-amino-5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}benzonitrile;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-chlorobenzene-1,3-diamine;(R)-4-(3-aminopiperidin-1-yl)-N-[4-methyl-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine;(R)—N-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;(R)-4-(3-aminopiperidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;(R)—N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;(R)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;(R)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;(R)—N-{1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-{1-[2-(4-fluoro-3-trifluoromethylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;(R)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;(R)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;(R)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;(R)-2-fluoro-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-2-methyl-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)—N¹-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;(R)—N¹-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;(R)-3-amino-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-(4-fluoro-3-trifluoromethylphenyl)-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amine;(R)—N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;(R)—N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;(R)—N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;(R)—N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;(R)-3-amino-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;(R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitrile;(R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-fluorobenzonitrile;(R)—N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;(S)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;(R)-5-({4-butyl-6-[3-(ethylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;(R)-5-({4-butyl-6-[3-(butylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;(R)-5-({4-butyl-6-[3-(pentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;(R)-5-({4-butyl-6-[3-(isobutylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;(R)-5-({4-butyl-6-[3-(isopentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;(R)-5-({4-butyl-6-[3-(neopentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;(R)-5-{[4-butyl-6-(3-{[3-(methylthio)propyl]amino}piperidin-1-yl)pyrimidin-2-yl]amino}-2-methylbenzonitrile;(R)-4-fluoro-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;(R)-4-chloro-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;(R)-2-amino-5-({4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}amino)benzonitrile;(R)—N-(3-methoxy-4-methylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;(R)-4-methyl-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;(R)-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;(R)-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-fluorobenzonitrile;(R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine;(R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;(R)-3-amino-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;(R)-2-amino-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;(R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-fluorobenzene-1,3-diamine;(R)-4-butyl-N-(3-methoxy-4-methylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;(R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-methylbenzene-1,3-diamine;(R)-4-butyl-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;(R)—N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;(R)—N-(3,4-dimethylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;(R)—N-(3-fluoro-4-methylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;(R)—N-[4-methyl-3-(trifluoromethyl)phenyl]-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;(R)-4-methoxy-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;(R)—N-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indazol-6-amine;(R)—N⁴-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,2,4-triamine;(R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;(R)-3-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;(R)-4-butyl-N-(3,4-dimethylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;(R)-4-butyl-N-(3-fluoro-4-methylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;(R)-4-butyl-N-[4-methyl-3-(trifluoromethyl)phenyl]-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;(R)—N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-methoxybenzene-1,3-diamine;(R)—N-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-1H-indazol-6-amine;(R)—N⁴-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}benzene-1,2,4-triamine;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-nitrophenyl)pyrimidin-2-amine;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-fluoro-3-nitrophenyl)pyrimidin-2-amine;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;(R)-3-amino-5-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-[4-methyl-3-(trifluoromethyl)phenyl]pyrimidin-2-amine;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-fluoro-4-methylphenyl)pyrimidin-2-amine;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-methoxy-4-methylphenyl)pyrimidin-2-amine;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-4-methylbenzene-1,3-diamine;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3,4-dimethylphenyl)pyrimidin-2-amine;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-[4-fluoro-3-(trifluoromethyl)phenyl]pyrimidin-2-amine;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;(R)-2-amino-5-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;(R)-3-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;(R)—N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]benzene-1,4-diamine;(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-chloro-3-nitrophenyl)pyrimidin-2-amine;and(R)—N⁴-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]benzene-1,2,4-triamine.